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The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions

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Abstract

Interleukin-1 (IL-1) includes a family of closely related genes; the two major agonistic proteins, IL-1α and IL-1β, are pleiotropic and affect mainly inflammation, immunity and hemopoiesis. The IL-1Ra antagonist is a physiological inhibitor of pre-formed IL-1. Recombinant IL-1α and IL-1β bind to the same receptors and induce the same biological functions. As such, the IL-1 molecules have been considered identical in normal homeostasis and in disease. However, the IL-1 molecules differ in their compartmentalization within the producing cell or the microenvironment. Thus, IL-1β is solely active in its secreted form, whereas IL-1α is mainly active in cell-associated forms (intracellular precursor and membrane-bound IL-1α) and only rarely as a secreted cytokine, as it is secreted only in a limited manner. IL-1 is abundant at tumor sites, where it may affect the process of carcinogenesis, tumor growth and invasiveness and also the patterns of tumor–host interactions. Here, we review the effects of microenvironment- and tumor cell-derived IL-1 on malignant processes in experimental tumor models and in cancer patients. We propose that membrane-associated IL-1α expressed on malignant cells stimulates anti-tumor immunity, while secretable IL-1β, derived from the microenvironment or the malignant cells, activates inflammation that promotes invasiveness and also induces tumor-mediated suppression. Inhibition of the function of IL-1 by the IL-1Ra, reduces tumor invasiveness and alleviates tumor-mediated suppression, pointing to its feasibility in cancer therapy. Differential manipulation of IL-1α and IL-1β in malignant cells or in the tumor’s microenvironment can open new avenues for using IL-1 in cancer therapy.

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References

  1. Nathan, C. (2002). Points of control in inflammation. Nature, 420, 846–852.

    Article  CAS  PubMed  Google Scholar 

  2. Clevers, H. (2004). At the crossroads of inflammation and cancer. Cell, 118, 671–674.

    Article  CAS  PubMed  Google Scholar 

  3. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet, 357, 539–545.

    Article  CAS  PubMed  Google Scholar 

  4. Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420, 860–867.

    Article  CAS  PubMed  Google Scholar 

  5. Coussens, L. M., & Werb, Z. (2001). Inflammatory cells and cancer: think different! Journal of Experimental Medicine, 193, F23–F26.

    Article  CAS  PubMed  Google Scholar 

  6. Cordon-Cardo, C., & Prives, C. (1999). At the crossroads of inflammation and tumorigenesis. Journal of Experimental Medicine, 190, 1367–1370.

    Article  CAS  PubMed  Google Scholar 

  7. Balkwill, F., Charles, K. A., & Mantovani, A. (2005). Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell, 7, 211–217.

    Article  CAS  PubMed  Google Scholar 

  8. Philip, M., Rowley, D. A., & Schreiber, H. (2004). Inflammation as a tumor promoter in cancer induction. Seminars in Cancer Biology, 14, 433–439.

    Article  CAS  PubMed  Google Scholar 

  9. Pollard, J. W. (2004). Tumour-educated macrophages promote tumour progression and metastasis. Nature Reviews, Cancer, 4, 71–78.

    Article  CAS  Google Scholar 

  10. Vakkila, J., & Lotze, M. T. (2004). Inflammation and necrosis promote tumour growth. Nature Reviews, Immunology, 4, 641–648.

    Article  CAS  Google Scholar 

  11. Dinarello, C. A., & Moldawer, L. L. (2002). Proinflammatory and anti-inflammatory cytokines in rheumatoid arthritis. A primer for clinicians, Third edition. Thousand Oaks, CA: Amgen, pp. 21–51.

    Google Scholar 

  12. Dinarello, C. A. (1996). Biologic basis for interleukin-1 in disease. Blood, 87, 2095–2147.

    CAS  PubMed  Google Scholar 

  13. Auron, P. E. (1998). The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine & Growth Factor Reviews, 9, 221–237.

    Article  CAS  Google Scholar 

  14. Martin, M. U., & Falk, W. (1997). The interleukin-1 receptor complex and interleukin-1 signal transduction. European Cytokine Network, 8, 5–17.

    CAS  PubMed  Google Scholar 

  15. Stylianou, E., & Saklatvala, J. (1998). Interleukin-1. International Journal of Biochemistry & Cell Biology, 30, 1075–1079.

    Article  CAS  Google Scholar 

  16. Mantovani, A., Muzio, M., Ghezzi, P., Colotta, C., & Introna, M. (1998). Regulation of inhibitory pathways of the interleukin-1 system. Annals of the New York Academy of Sciences, 840, 338–351.

    Article  CAS  PubMed  Google Scholar 

  17. Dinarello, C. A. (2005). Blocking IL-1 in systemic inflammation. JEM, 201, 1355–1359.

    Article  CAS  Google Scholar 

  18. Kawai, T., & Akira, S. (2006). TLR signaling. Cell Death and Differentiation.

  19. O‘Neill, L. A. (2006). How Toll-like receptors signal: what we know and what we don't know. Current Opinion in Immunology, 18, 3–9.

    Article  PubMed  CAS  Google Scholar 

  20. Hacham, M., Argov, S., White, R. M., Segal, S., & Apte, R. N. (2002). Different patterns of interleukin-1alpha and interleukin-1beta expression in organs of normal young and old mice. European Cytokine Network, 13, 55–65.

    CAS  PubMed  Google Scholar 

  21. Hacham, M., Argov, S., White, R. M., Segal, S., & Apte, R. N. (2000). Distinct patterns of IL-1 alpha and IL-1 beta organ distribution – a possible basis for organ mechanisms of innate immunity. Advances in Experimental Medicine and Biology, 479, 185–202.

    CAS  PubMed  Google Scholar 

  22. Apte, R. N., & Voronov, E. (2002). Interleukin-1-a major pleiotropic cytokine in tumor–host interactions. Seminars in Cancer Biology, 12, 277–290.

    Article  CAS  PubMed  Google Scholar 

  23. Douvdevani, A., Huleihel, M., Zoller, M., Segal, S., & Apte, R. N. (1992). Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1 alpha either spontaneously or following IL-1 alpha gene transfer. International Journal of Cancer, 51, 822–830.

    CAS  Google Scholar 

  24. Zoller, M., Douvdevani, A., Segal, S., & Apte, R. N. (1992). Interleukin-1 production by transformed fibroblasts. II. Influence on antigen presentation and T-cell-mediated anti-tumor response. International Journal of Cancer, 50, 450–457.

    CAS  Google Scholar 

  25. Zoller, M., Douvdevani, A., Segal, S., & Apte, R. N. (1992). Interleukin-1 produced by tumorigenic fibroblasts influences tumor rejection. International Journal of Cancer, 50, 443–449.

    CAS  Google Scholar 

  26. Apte, R. N., Douvdevani, A., Zoller, M., White, R. M., Dvorkin, T., Shimoni, N., et al. (1993). Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity. Immunology Letters, 39, 45–52.

    Article  CAS  PubMed  Google Scholar 

  27. Apte, R. N., Dvorkin, T., Song, X., Fima, E., Krelin, Y., Yulevitch, A., et al. (2000). Opposing effects of IL-1 alpha and IL-1 beta on malignancy patterns. Tumor cell-associated IL-1 alpha potentiates anti-tumor immune responses and tumor regression, whereas IL-1 beta potentiates invasiveness. Advances in Experimental Medicine and Biology, 479, 277–288.

    CAS  PubMed  Google Scholar 

  28. Voronov, E., Weinstein, Y., Benharroch, D., Cagnano, E., Ofir, R., Dobkin, M., et al. (1999). Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells that display short-term interleukin 1alpha expression. Cancer Research, 59, 1029–1035.

    CAS  PubMed  Google Scholar 

  29. Song, X., Voronov, E., Dvorkin, T., Fima, E., Cagnano, E., Benharroch, D., et al. (2003). Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness. Journal of Immunology, 171, 6448–6456.

    CAS  Google Scholar 

  30. Werman, A., Werman-Venkert, R., White, R., Lee, J. K., Werman, B., Krelin, Y., et al. (2004). The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription. Proceedings of the National Academy of Sciences of the United States of America, 101, 2434–2439.

    Article  CAS  PubMed  Google Scholar 

  31. Song, X., Krelin, Y., Dvorkin, T., Bjorkdahl, O., Segal, S., Dinarello, C. A., et al. (2005). CD11b+/Gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1{beta}-secreting cells. Journal of Immunology, 175, 8200–8208.

    CAS  Google Scholar 

  32. Miller, L. S., O‘Connell, R. M., Gutierrez, M. A., Pietras, E. M., Shahangian, A., Gross, C. E., et al. (2006). MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity, 24, 79–91.

    Article  CAS  PubMed  Google Scholar 

  33. Mizel, S. B. (1982). Interleukin 1 and T cell activation. Immunological Reviews, 63, 51–72.

    Article  CAS  PubMed  Google Scholar 

  34. Shibuya, K., Robinson, D., Zonin, F., Hartley, S. B., Macatonia, S. E., Somoza, C., et al. (1998). IL-1 alpha and TNF-alpha are required for IL-12-induced development of Th1 cells producing high levels of IFN-gamma in BALB/c but not C57BL/6 mice. Journal of Immunology, 160, 1708–1716.

    CAS  Google Scholar 

  35. Weaver, C. T., Hawrylowicz, C. M., & Unanue, E. R. (1988). T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proceedings of the National Academy of Sciences of the United States of America, 85, 8181–8185.

    Article  CAS  PubMed  Google Scholar 

  36. McArthur, J. G., & Raulet, D. H. (1993). CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4. Journal of Experimental Medicine, 178, 1645–1653.

    Article  CAS  PubMed  Google Scholar 

  37. Greenbaum, L. A., Horowitz, J. B., Woods, A., Pasqualini, T., Reich, E. P., & Bottomly, K. (1988). Autocrine growth of CD4+ T cells. Differential effects of IL-1 on helper and inflammatory T cells. Journal of Immunology, 140, 1555–1560.

    CAS  Google Scholar 

  38. Lichtman, A. H., Chin, J., Schmidt, J. A., & Abbas, A. K. (1988). Role of interleukin 1 in the activation of T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 85, 9699–9703.

    Article  CAS  PubMed  Google Scholar 

  39. Von Stebut, E., Ehrchen, J. M., Belkaid, Y., Kostka, S. L., Molle, K., Knop, J., et al. (2003). Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. Journal of Experimental Medicine, 198, 191–199.

    Article  CAS  Google Scholar 

  40. Filippi, C., Hugues, S., Cazareth, J., Julia, V., Glaichenhaus, N., & Ugolini, S. (2003). CD4+ T cell polarization in mice is modulated by strain-specific major histocompatibility complex-independent differences within dendritic cells. Journal of Experimental Medicine, 198, 201–209.

    Article  CAS  PubMed  Google Scholar 

  41. Eriksson, U., Kurrer, M. O., Sonderegger, I., Iezzi, G., Tafuri, A., Hunziker, L., et al. (2003). Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis. Journal of Experimental Medicine, 197, 323–331.

    Article  CAS  PubMed  Google Scholar 

  42. Su, S. B., Silver, P. B., Grajewski, R. S., Agarwal, R. K., Tang, J., Chan, C. C., et al. (2005). Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity. Journal of Immunology, 175, 6303–6310.

    CAS  Google Scholar 

  43. Nakata, Y., Matsuda, K., Uzawa, A., Nomura, M., Akashi, M., & Suzuki, G. (1995). Administration of recombinant human IL-1 by Staphylococcus enterotoxin B prevents tolerance induction in vivo. Journal of Immunology, 155, 4231–4235.

    CAS  Google Scholar 

  44. Mochizuki, D. Y., Eisenman, J. R., Conlon, P. J., Larsen, A. D., & Tushinski, R. J. (1987). Interleukin 1 regulates hematopoietic activity, a role previously ascribed to hemopoietin 1. Proceedings of the National Academy of Sciences of the United States of America, 84, 5267–5271.

    Article  CAS  PubMed  Google Scholar 

  45. Neta, R., Douches, S., & Oppenheim, J. J. (1986). Interleukin 1 is a radioprotector. Journal of Immunology, 136, 2483–2485.

    CAS  Google Scholar 

  46. Buryskova, M., Pospisek, M., Grothey, A., Simmet, T., & Burysek, L. (2004). Intracellular interleukin-1alpha functionally interacts with histone acetyltransferase complexes. Journal of Biological Chemistry, 279, 4017–4026.

    Article  CAS  PubMed  Google Scholar 

  47. Wessendorf, J. H., Garfinkel, S., Zhan, X., Brown, S., & Maciag, T. (1993). Identification of a nuclear localization sequence within the structure of the human interleukin-1 alpha precursor. Journal of Biological Chemistry, 268, 22100–22104.

    CAS  PubMed  Google Scholar 

  48. Maier, J. A., Statuto, M., & Ragnotti, G. (1994). Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells. Molecular and Cellular Biology, 14, 1845–1851.

    CAS  PubMed  Google Scholar 

  49. Maier, J. A., Voulalas, P., Roeder, D., & Maciag, T. (1990). Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. Science, 249, 1570–1574.

    Article  CAS  PubMed  Google Scholar 

  50. Cozzolino, F., Torcia, M., Aldinucci, D., Ziche, M., Almerigogna, F., Bani, D., et al. (1990). Interleukin 1 is an autocrine regulator of human endothelial cell growth. Proceedings of the National Academy of Sciences of the United States of America, 87, 6487–6491.

    Article  CAS  PubMed  Google Scholar 

  51. Garfinkel, S., Haines, D. S., Brown, S., Wessendorf, J., Gillespie, D. H., & Maciag, T. (1992). Interleukin-1 alpha mediates an alternative pathway for the antiproliferative action of poly(I.C) on human endothelial cells. Journal of Biological Chemistry, 267, 24375–24378.

    CAS  PubMed  Google Scholar 

  52. Kumar, S., Millis, A. J., & Baglioni, C. (1992). Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 89, 4683–4687.

    Article  CAS  PubMed  Google Scholar 

  53. Beasley, D., & Cooper, A. L. (1999). Constitutive expression of interleukin-1alpha precursor promotes human vascular smooth muscle cell proliferation. American Journal of Physiology, 276, H901–H912.

    CAS  PubMed  Google Scholar 

  54. Kupper, T. S., Chua, A. O., Flood, P., McGuire, J., & Gubler, U. (1987). Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation. Journal of Clinical Investigation, 80, 430–436.

    Article  CAS  PubMed  Google Scholar 

  55. Sauder, D. N., Stanulis-Praeger, B. M., & Gilchrest, B. A. (1988). Autocrine growth stimulation of human keratinocytes by epidermal cell-derived thymocyte-activating factor: implications for skin aging. Archives of Dermatological Research, 280, 71–76.

    Article  CAS  PubMed  Google Scholar 

  56. Burysek, L., & Houstek, J. (1996). Multifactorial induction of gene expression and nuclear localization of mouse interleukin 1 alpha. Cytokine, 8, 460–467.

    Article  CAS  PubMed  Google Scholar 

  57. Douvdevani, A., Huleihel, M., Segal, S., & Apte, R. N. (1991). Aberrations in interleukin-1 expression in oncogene-transformed fibrosarcoma lines: constitutive interleukin-1 alpha transcription and manifestation of biological activity. European Cytokine Network, 2, 257–264.

    CAS  PubMed  Google Scholar 

  58. Dvorkin, T., Song, X., Argov, S., White, R. M., Zoller, M., Segal, S., et al. (2006). Immune phenomena that are involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1a. Journal of Leukocyte Biology, 80, 96–106.

    Article  CAS  PubMed  Google Scholar 

  59. Apte, R. N., Krelin, Y., Song, X., Dotan, S., Recih, E., Elkabets, M., et al. (2006). Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour–host interactions. European Journal of Cancer, 42, 751–759.

    Article  CAS  PubMed  Google Scholar 

  60. Dumitriu, I. E., Baruah, P., Valentinis, B., Voll, R. E., Herrmann, M., Nawroth, P. P., et al. (2005). Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. Journal of Immunology, 174, 7506–7515.

    CAS  Google Scholar 

  61. Lotze, M. T., & Tracey, K. J. (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Reviews, Immunology, 5, 331–342.

    Article  CAS  Google Scholar 

  62. Horai, R., Asano, M., Sudo, K., Kanuka, H., Suzuki, M., Nishihara, M., et al. (1998). Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion. Journal of Experimental Medicine, 187, 1463–1475.

    Article  CAS  PubMed  Google Scholar 

  63. Horai, R., Saijo, S., Tanioka, H., Nakae, S., Sudo, K., Okahara, A., et al. (2000). Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. Journal of Experimental Medicine, 191, 313–320.

    Article  CAS  PubMed  Google Scholar 

  64. Iwakura, Y. (2002). Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models. Cytokine & Growth Factor Reviews, 13, 341–355.

    Article  CAS  Google Scholar 

  65. Nicklin, M. J., Hughes, D. E., Barton, J. L., Ure, J. M., & Duff, G. W. (2000). Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. Journal of Experimental Medicine, 191, 303–312.

    Article  CAS  PubMed  Google Scholar 

  66. Nakae, S., Asano, M., Horai, R., & Iwakura, Y. (2001). Interleukin-1 beta, but not interleukin-1 alpha, is required for T-cell-dependent antibody production. Immunology, 104, 402–409.

    Article  CAS  PubMed  Google Scholar 

  67. Nakae, S., Asano, M., Horai, R., Sakaguchi, N., & Iwakura, Y. (2001). IL-1 enhances T cell-dependent antibody production through induction of CD40 ligand and OX40 on T cells. Journal of Immunology, 167, 90–97.

    CAS  Google Scholar 

  68. Nakae, S., Naruse-Nakajima, C., Sudo, K., Horai, R., Asano, M., & Iwakura, Y. (2001). IL-1 alpha, but not IL-1 beta, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity. International Immunology, 13, 1471–1478.

    Article  CAS  PubMed  Google Scholar 

  69. Voronov, E., Dayan, M., Zinger, H., Gayvoronsky, L., Lin, J-P., Iwakura, Y., et al. (2006). IL-1beta deficient mice are resistant to induction of experimental SLE. European Cytokine Network, 17, 109–116.

    CAS  PubMed  Google Scholar 

  70. Lee, W. Y., Fischer, S. M., Butler, A. P., & Locniskar, M. F. (1993). Modulation of interleukin-1 alpha mRNA expression in mouse epidermis by tumor promoters and antagonists. Molecular Carcinogenesis, 7, 26–35.

    CAS  PubMed  Google Scholar 

  71. Oberyszyn, T. M., Sabourin, C. L., Bijur, G. N., Oberyszyn, A. S., Boros, L. G., & Robertson, F. M. (1993). Interleukin-1 alpha gene expression and localization of interleukin-1 alpha protein during tumor promotion. Molecular Carcinogenesis, 7, 238–248.

    CAS  PubMed  Google Scholar 

  72. La, E., Muga, S. J., Locniskar, M. F., & Fischer, S. M. (1999). Altered expression of interleukin-1 receptor antagonist in different stages of mouse skin carcinogenesis. Molecular Carcinogenesis, 24, 276–286.

    Article  CAS  PubMed  Google Scholar 

  73. Scott, K. A., Arnott, C. H., Robinson, S. C., Moore, R. J., Thompson, R. G., Marshall, J. F., et al. (2004). TNF-alpha regulates epithelial expression of MMP-9 and integrin alphavbeta6 during tumour promotion. A role for TNF-alpha in keratinocyte migration? Oncogene, 23, 6954–6966.

    Article  CAS  PubMed  Google Scholar 

  74. Scott, K. A., Moore, R. J., Arnott, C. H., East, N., Thompson, R. G., Scallon, B. J., et al. (2003). An anti-tumor necrosis factor-alpha antibody inhibits the development of experimental skin tumors. Mol Cancer Ther, 2, 445–451.

    CAS  PubMed  Google Scholar 

  75. Arnott, C. H., Scott, K. A., Moore, R. J., Hewer, A., Phillips, D. H., Parker, P., et al. (2002). Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha- and AP-1-dependent pathway. Oncogene, 21, 4728–4738.

    Article  CAS  PubMed  Google Scholar 

  76. Suganuma, M., Okabe, S., Marino, M. W., Sakai, A., Sueoka, E., & Fujiki, H. (1999). Essential role of tumor necrosis factor alpha (TNF-alpha) in tumor promotion as revealed by TNF-alpha-deficient mice. Cancer Research, 59, 4516–4518.

    CAS  PubMed  Google Scholar 

  77. Balkwill, F. (2002). Tumor necrosis factor or tumor promoting factor? Cytokine & Growth Factor Reviews, 13, 135–141.

    Article  CAS  Google Scholar 

  78. Szlosarek, P. W., & Balkwill, F. R. (2003). Tumour necrosis factor alpha: a potential target for the therapy of solid tumours. Lancet Oncology, 4, 565–573.

    Article  CAS  PubMed  Google Scholar 

  79. Knight, B., Yeoh, G. C., Husk, K. L., Ly, T., Abraham, L. J., Yu, C., et al. (2000). Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. Journal of Experimental Medicine, 192, 1809–1818.

    Article  CAS  PubMed  Google Scholar 

  80. Li, X., Eckard, J., Shah, R., Malluck, C., & Frenkel, K. (2002). Interleukin-1alpha up-regulation in vivo by a potent carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) and control of DMBA-induced inflammatory responses. Cancer Research, 62, 417–423.

    CAS  PubMed  Google Scholar 

  81. Qin, Z., Kim, H. J., Hemme, J., & Blankenstein, T. (2002). Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma receptor-dependent foreign body reaction. Journal of Experimental Medicine, 195, 1479–1490.

    Article  CAS  PubMed  Google Scholar 

  82. Blankenstein, T., & Qin, Z. (2003). Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance. Advances in Cancer Research, 90, 179–207.

    Article  CAS  PubMed  Google Scholar 

  83. Blankenstein, T., & Qin, Z. (2003). The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis. Current Opinion in Immunology, 15, 148–154.

    Google Scholar 

  84. Murphy, J. E., Morales, R. E., Scott, J., & Kupper, T. S. (2003). IL-1 alpha, innate immunity, and skin carcinogenesis: The effect of constitutive expression of IL-1 alpha in epidermis on chemical carcinogenesis. Journal of Immunology, 170, 5697–5703.

    CAS  Google Scholar 

  85. Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., et al. (2004). NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature, 431, 461–466.

    Article  CAS  PubMed  Google Scholar 

  86. Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z. W., Egan, L. J., et al. (2004). IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell, 118, 285–296.

    Article  CAS  PubMed  Google Scholar 

  87. Lin, A., & Karin, M. (2003). NF-kappaB in cancer: a marked target. Seminars in Cancer Biology, 13, 107–114.

    Article  CAS  PubMed  Google Scholar 

  88. Amit, S., & Ben-Neriah, Y. (2003). NF-kappaB activation in cancer: a challenge for ubiquitination – and proteasome-based therapeutic approach. Seminars in Cancer Bioliology, 13, 15–28.

    Article  CAS  PubMed  Google Scholar 

  89. Stevenson, F. T., Turck, J., Locksley, R. M., & Lovett, D. H. (1997). The N-terminal propiece of interleukin 1 alpha is a transforming nuclear oncoprotein. Proceedings of the National Academy of Sciences of the United States of America, 94, 508–513.

    Article  CAS  PubMed  Google Scholar 

  90. Pollock, A. S., Turck, J., & Lovett, D. H. (2003). The prodomain of interleukin 1alpha interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells. FASEB Journal, 17, 203–213.

    Article  CAS  PubMed  Google Scholar 

  91. Silver, A., Boultwood, J., Breckon, G., Masson, W., Adam, J., Shaw, A. R., et al. (1989). Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: a candidate initiating event for murine radiation-myeloid leukemogenesis? Molecular Carcinogenesis, 2, 226–232.

    CAS  PubMed  Google Scholar 

  92. Vanhamme, L., Marshall, G. M., Schuh, A. C., Breitman, M. L., & Vogt, P. K. (1993). Tumor necrosis factor alpha and interleukin 1 alpha induce anchorage independence in v-jun transgenic murine cells. Cancer Research, 53, 615–621.

    CAS  PubMed  Google Scholar 

  93. Vale, T., Ngo, T. T., White, M. A., & Lipsky, P. E. (2001). Raf-induced transformation requires an interleukin 1 autocrine loop. Cancer Research, 61, 602–607.

    CAS  PubMed  Google Scholar 

  94. Beaupre, D. M., Talpaz, M., Marini, F. C., 3rd, Cristiano, R. J., Roth, J. A., Estrov, Z., et al. (1999). Autocrine interleukin-1beta production in leukemia: evidence for the involvement of mutated RAS. Cancer Research, 59, 2971–2980.

    CAS  PubMed  Google Scholar 

  95. Castelli, C., Sensi, M., Lupetti, R., Mortarini, R., Panceri, P., Anichini, A., et al. (1994). Expression of interleukin 1 alpha, interleukin 6, and tumor necrosis factor alpha genes in human melanoma clones is associated with that of mutated N-RAS oncogene. Cancer Research, 54, 4785–4790.

    CAS  PubMed  Google Scholar 

  96. Dvorak, H. F. (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. New England Journal of Medicine, 315, 1650–1659.

    Article  CAS  PubMed  Google Scholar 

  97. Radisky, D., Hagios, C., & Bissell, M. J. (2001). Tumors are unique organs defined by abnormal signaling and context. Seminars in Cancer Biology, 11, 87–95.

    Article  CAS  PubMed  Google Scholar 

  98. Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., et al. (2005). Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 121, 335–348.

    Article  CAS  PubMed  Google Scholar 

  99. Hill, R., Song, Y., Cardiff, R. D., & Van Dyke, T. (2005). Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell, 123, 1001–1011.

    Article  CAS  PubMed  Google Scholar 

  100. Stetler-Stevenson, W. G., & Yu, A. E. (2001). Proteases in invasion: matrix metalloproteinases. Seminars in Cancer Biology, 11, 143–152.

    Article  CAS  PubMed  Google Scholar 

  101. Strieter, R. M., Polverini, P. J., Arenberg, D. A., Walz, A., Opdenakker, G., Van Damme, J., et al. (1995). Role of C-X-C chemokines as regulators of angiogenesis in lung cancer. Journal of Leukocyte Biology, 57, 752–762.

    CAS  PubMed  Google Scholar 

  102. Mantovani, A., & Dejana, E. (1989). Cytokines as communication signals between leukocytes and endothelial cells. Immunology Today, 10, 370–375.

    Article  CAS  PubMed  Google Scholar 

  103. Folkman, J., & D'Amore, P. A. (1996). Blood vessel formation: What is its molecular basis? Cell, 87, 1153–1155.

    Article  CAS  PubMed  Google Scholar 

  104. Vidal-Vanaclocha, F., Amezaga, C., Asumendi, A., Kaplanski, G., & Dinarello, C. A. (1994). Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases. Cancer Research, 54, 2667–2672.

    CAS  PubMed  Google Scholar 

  105. Vidal-Vanaclocha, F., Alvarez, A., Asumendi, A., Urcelay, B., Tonino, P., & Dinarello, C. A. (1996). Interleukin 1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1-induced mannose receptors and growth factor production in vitro. Journal of the National Cancer Institute, 88, 198–205.

    CAS  PubMed  Google Scholar 

  106. Vidal-Vanaclocha, F., Fantuzzi, G., Mendoza, L., Fuentes, A. M., Anasagasti, M. J., Martin, J., et al. (2000). IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proceedings of the National Academy of Sciences of the United States of America, 97, 734–739.

    Article  CAS  PubMed  Google Scholar 

  107. Bertomeu, M. C., Gallo, S., Lauri, D., Haas, T. A., Orr, F. W., Bastida, E., et al. (1993). Interleukin 1-induced cancer cell/endothelial cell adhesion in vitro and its relationship to metastasis in vivo: role of vessel wall 13-HODE synthesis and integrin expression. Clinical & Experimental Metastasis, 11, 243–250.

    Article  CAS  Google Scholar 

  108. Carrascal, M. T., Mendoza, L., Valcarcel, M., Salado, C., Egilegor, E., Telleria, N., et al. (2003). Interleukin-18 binding protein reduces b16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium. Cancer Research, 63, 491–497.

    CAS  PubMed  Google Scholar 

  109. Voronov, E., Shouval, D. S., Krelin, Y., Cagnano, E., Benharroch, D., Iwakura, Y., et al. (2003). IL-1 is required for tumor invasiveness and angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 100, 2645–2650.

    Article  CAS  PubMed  Google Scholar 

  110. Scherbarth, S., & Orr, F. W. (1997). Intravital videomicroscopic evidence for regulation of metastasis by the hepatic microvasculature: effects of interleukin-1alpha on metastasis and the location of B16F1 melanoma cell arrest. Cancer Research, 57, 4105–4110.

    CAS  PubMed  Google Scholar 

  111. McKenzie, R. C., Oran, A., Dinarello, C. A., & Sauder, D. N. (1996). Interleukin-1 receptor antagonist inhibits subcutaneous B16 melanoma growth in vivo. Anticancer Research, 16, 437–441.

    CAS  PubMed  Google Scholar 

  112. Chirivi, R. G., Garofalo, A., Padura, I. M., Mantovani, A., & Giavazzi, R. (1993). Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system. Cancer Research, 53, 5051–5054.

    CAS  PubMed  Google Scholar 

  113. Anasagasti, M. J., Olaso, E., Calvo, F., Mendoza, L., Martin, J. J., Bidaurrazaga, J., et al. (1997). Interleukin 1-dependent and -independent mouse melanoma metastases. Journal of the National Cancer Institute, 89, 645–651.

    Article  CAS  PubMed  Google Scholar 

  114. Nakao, S., Kuwano, T., Tsutsumi-Miyahara, C., Ueda, S., Kimura, Y. N., Hamano, S., et al. (2005). Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. Journal of Clinical Investigation, 115, 2979–2991.

    Article  CAS  PubMed  Google Scholar 

  115. Mantovani, A., Allavena, P., & Sica, A. (2004). Tumour-associated macrophages as a prototypic type II polarised phagocyte population: Role in tumour progression. European Journal of Cancer, 40, 1660–1667.

    Article  CAS  PubMed  Google Scholar 

  116. Jung, Y. J., Isaacs, J. S., Lee, S., Trepel, J., Neckers, L. (2003). IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB Journal, 17, 2115–2117.

    CAS  PubMed  Google Scholar 

  117. Bar, D., Apte, R. N., Voronov, E., Dinarello, C. A., & Cohen, S. (2004). A continuous delivery system of IL-1 receptor antagonist reduces angiogenesis and inhibits tumor development. FASEB Journal, 18, 161–163.

    CAS  PubMed  Google Scholar 

  118. Elaraj, D. M., Weinreich, D. M., Varghese, S., Puhlmann, M., Hewitt, S. M., Carroll, N. M., et al. (2006). The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clinical Cancer Research, 12, 1088–1096.

    Article  CAS  PubMed  Google Scholar 

  119. Weinreich, D. M., Elaraj, D. M., Puhlmann, M., Hewitt, S. M., Carroll, N. M., Feldman, E. D., et al. (2003). Effect of interleukin 1 receptor antagonist gene transduction on human melanoma xenografts in nude mice. Cancer Research, 63, 5957–5961.

    CAS  PubMed  Google Scholar 

  120. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunology, 3, 991–998.

    Article  CAS  PubMed  Google Scholar 

  121. Ikeda, H., Old, L. J., & Schreiber, R. D. (2002). The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine & Growth Factor Reviews, 13, 95–109.

    Article  CAS  Google Scholar 

  122. Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 21, 137–148.

    Article  CAS  PubMed  Google Scholar 

  123. Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The three Es of cancer immunoediting. Annual Review of Immunology, 22, 329–360.

    Article  CAS  PubMed  Google Scholar 

  124. Estrov, Z., Kurzrock, R., Estey, E., Wetzler, M., Ferrajoli, A., Harris, D., et al. (1992). Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors. Blood, 79, 1938–1945.

    CAS  PubMed  Google Scholar 

  125. Estrov, Z., Black, R. A., Sleath, P. R., Harris, D., Van, Q., LaPushin, R., et al. (1995). Effect of interleukin-1 beta converting enzyme inhibitor on acute myelogenous leukemia progenitor proliferation. Blood, 86, 4594–4602.

    CAS  PubMed  Google Scholar 

  126. Rambaldi, A., Torcia, M., Dinarello, C. A., Barbui, T., & Cozzolino, F. (1993). Modulation of cell proliferation and cytokine production in AML by recombinant interleukin-1 receptor antagonist. Leukemia, 7(Suppl 2), S10–S12.

    PubMed  Google Scholar 

  127. Schiro, R., Longoni, D., Rossi, V., Maglia, O., Doni, A., Arsura, M., et al. (1994). Suppression of juvenile chronic myelogenous leukemia colony growth by interleukin-1 receptor antagonist. Blood, 83, 460–465.

    CAS  PubMed  Google Scholar 

  128. Stosic-Grujicic, S., Basara, N., Milenkovic, P., & Dinarello, C. A. (1995). Modulation of acute myeloblastic leukemia (AML) cell proliferation and blast colony formation by antisense oligomer for IL-1 beta converting enzyme (ICE) and IL-1 receptor antagonist (IL-1ra). Journal of Chemotherapy, 7, 67–70.

    CAS  PubMed  Google Scholar 

  129. Stosic-Grujicic, S., Basara, N., & Dinarello, C. A. (1999). Modulatory in vitro effects of interleukin-1 receptor antagonist (IL-1Ra) or antisense oligonucleotide to interleukin-1 beta converting enzyme (ICE) on acute myeloid leukaemia (AML) cell growth. Clinical and Laboratory Haematology, 21, 173–185.

    Article  CAS  PubMed  Google Scholar 

  130. Wetzler, M., Kurzrock, R., Estrov, Z., Kantarjian, H., Gisslinger, H., Underbrink, M. P., et al. (1994). Altered levels of interleukin-1 beta and interleukin-1 receptor antagonist in chronic myelogenous leukemia: clinical and prognostic correlates. Blood, 84, 3142–3147.

    CAS  PubMed  Google Scholar 

  131. Lazar-Molnar, E., Hegyesi, H., Toth, S., & Falus, A. (2000). Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine, 12, 547–554.

    Article  CAS  PubMed  Google Scholar 

  132. Nozaki, S., Sledge, G. W., Jr., & Nakshatri, H. (2000). Cancer cell-derived interleukin 1alpha contributes to autocrine and paracrine induction of pro-metastatic genes in breast cancer. Biochemical and Biophysical Research Communications, 275, 60–62.

    Article  CAS  PubMed  Google Scholar 

  133. Hayashi, H., Shimizu, R., Fujii, K., Itoh, S., Yang, D., & Onozaki, K. (1997). Resistance to IL-1 anti-proliferative effect, accompanied by characteristics of advanced melanoma, permits invasion of human melanoma cells in vitro, but not metastasis in the nude mouse. International Journal of Cancer, 71, 416–421.

    Article  CAS  Google Scholar 

  134. Torisu, H., Ono, M., Kiryu, H., Furue, M., Ohmoto, Y., Nakayama, J., et al. (2000). Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFalpha and IL-1alpha. International Journal of Cancer, 85, 182–188.

    CAS  Google Scholar 

  135. Hoosein, N. M. (1998). Neuroendocrine and immune mediators in prostate cancer progression. Front Bioscience, 3, D1274–D1279.

    CAS  Google Scholar 

  136. Culig, Z., Hobisch, A., Herold, M., Hittmair, A., Thurnher, M., Eder, I. E., et al. (1998). Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells. British Journal of Cancer, 78, 1004–1011.

    CAS  PubMed  Google Scholar 

  137. Chiao, J. W., Hsieh, T. C., Xu, W., Sklarew, R. J., & Kancherla, R. (1999). Development of human prostate cancer cells to neuroendocrine-like cells by interleukin-1. International Journal of Oncology, 15, 1033–1037.

    CAS  PubMed  Google Scholar 

  138. Jin, L., Yuan, R. Q., Fuchs, A., Yao, Y., Joseph, A., Schwall, R., et al. (1997). Expression of interleukin-1beta in human breast carcinoma. Cancer, 80, 421–434.

    Article  CAS  PubMed  Google Scholar 

  139. Miller, L. J., Kurtzman, S. H., Anderson, K., Wang, Y., Stankus, M., Renna, M., et al. (2000). Interleukin-1 family expression in human breast cancer: interleukin-1 receptor antagonist. Cancer Investigation, 18, 293–302.

    CAS  PubMed  Google Scholar 

  140. Pantschenko, A. G., Pushkar, I., Anderson, K. H., Wang, Y., Miller, L. J., Kurtzman, S. H., et al. (2003). The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression. International Journal of Oncology, 23, 269–284.

    CAS  PubMed  Google Scholar 

  141. Palmieri, C., Roberts-Clark, D., Assadi-Sabet, A., Coope, R. C., O‘Hare, M., Sunters, A., et al. (2003). Fibroblast growth factor 7, secreted by breast fibroblasts, is an interleukin-1beta-induced paracrine growth factor for human breast cells. Journal of Endocrinology, 177, 65–81.

    Article  CAS  PubMed  Google Scholar 

  142. Tomimatsu, S., Ichikura, T., & Mochizuki, H. (2001). Significant correlation between expression of interleukin-1alpha and liver metastasis in gastric carcinoma. Cancer, 91, 1272–1276.

    Article  CAS  PubMed  Google Scholar 

  143. Iizuka, N., Hazama, S., Hirose, K., Abe, T., Tokuda, N., Fukumoto, T., et al. (1999). Interleukin-1 receptor antagonist mRNA expression and the progression of gastric carcinoma. Cancer Letter, 142, 179–184.

    Article  CAS  Google Scholar 

  144. Zambon, C. F., Basso, D., Navaglia, F., Belluco, C., Falda, A., Fogar, P., et al. (2005). Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome. Cytokine, 29, 141–152.

    Article  CAS  PubMed  Google Scholar 

  145. Sehouli, J., Mustea, A., Konsgen, D., Katsares, I., & Lichtenegger, W. (2002). Polymorphism of IL-1 receptor antagonist gene: role in cancer. Anticancer Research, 22, 3421–3424.

    CAS  PubMed  Google Scholar 

  146. Ilyin, S. E., Gonzalez-Gomez, I., Romanovicht, A., Gayle, D., Gilles, F. H., & Plata-Salaman, C. R. (2000). Autoregulation of the interleukin-1 system and cytokine-cytokine interactions in primary human astrocytoma cells. Brain Research Bulletin, 51, 29–34.

    Article  CAS  PubMed  Google Scholar 

  147. Oelmann, E., Kraemer, A., Serve, H., Reufi, B., Oberberg, D., Patt, S., et al. (1997). Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1. International Journal of Cancer, 71, 1066–1076.

    Article  CAS  Google Scholar 

  148. Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996). CD28/B7 system of T cell costimulation. Annual Review of Immunology, 14, 233–258.

    Article  CAS  PubMed  Google Scholar 

  149. Chambers, C. A., & Allison, J. P. (1999). Costimulatory regulation of T cell function. Current Opinion in Cell Biology, 11, 203–210.

    Article  CAS  PubMed  Google Scholar 

  150. Kalli, K., Huntoon, C., Bell, M., & McKean, D. J. (1998). Mechanism responsible for T-cell antigen receptor- and CD28- or interleukin 1 (IL-1) receptor-initiated regulation of IL-2 gene expression by NF-kappaB. Molecular and Cellular Biology, 18, 3140–3148.

    CAS  PubMed  Google Scholar 

  151. el-Shami, K. M., Tzehoval, E., Vadai, E., Feldman, M., & Eisenbach, L. (1999). Induction of antitumor immunity with modified autologous cells expressing membrane-bound murine cytokines. Journal of Interferon & Cytokine Research, 19, 1391–1401.

    Article  CAS  Google Scholar 

  152. Marr, R. A., Addison, C. L., Snider, D., Muller, W. J., Gauldie, J., & Graham, F. L. (1997). Tumour immunotherapy using an adenoviral vector expressing a membrane-bound mutant of murine TNF alpha. Gene Therapy, 4, 1181–1188.

    Article  CAS  PubMed  Google Scholar 

  153. Soo Hoo, W., Lundeen, K. A., Kohrumel, J. R., Pham, N. L., Brostoff, S. W., Bartholomew, R. M., et al. (1999). Tumor cell surface expression of granulocyte-macrophage colony-stimulating factor elicits antitumor immunity and protects from tumor challenge in the P815 mouse mastocytoma tumor model. Journal of Immunology, 162, 7343–7349.

    CAS  Google Scholar 

  154. Thompson, R. C., Pardoll, D. M., Jaffee, E. M., Ewend, M. G., Thomas, M. C., Tyler, B. M., et al. (1996). Systemic and local paracrine cytokine therapies using transduced tumor cells are synergistic in treating intracranial tumors. Journal of Immunotherapy with Emphasis on Tumor Immunology, 19, 405–413.

    CAS  PubMed  Google Scholar 

  155. Chirivi, R. G., Chiodoni, C., Musiani, P., Garofalo, A., Bernasconi, S., Colombo, M. P., et al. (1996). IL-1alpha gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice. International Journal of Cancer, 67, 856–863.

    Article  CAS  Google Scholar 

  156. Esandi, M. C., van Someren, G. D., Bout, A., Mulder, A. H., van Bekkum, D. W., Valerio, D., et al. (1998). IL-1/IL-3 gene therapy of non-small cell lung cancer (NSCLC) in rats using ‘cracked’ adenoproducer cells. Gene Therapy, 5, 778–788.

    Article  CAS  PubMed  Google Scholar 

  157. Bunt, S. K., Sinha, P., Clements, V. K., Leips, J., & Ostrand-Rosenberg, S. (2006). Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. Journal of Immunology, 176, 284–290.

    CAS  Google Scholar 

  158. Saijo, Y., Tanaka, M., Miki, M., Usui, K., Suzuki, T., Maemondo, M., et al. (2002). Proinflammatory cytokine IL-1 beta promotes tumor growth of Lewis lung carcinoma by induction of angiogenic factors: in vivo analysis of tumor–stromal interaction. Journal of Immunology, 169, 469–475.

    CAS  Google Scholar 

  159. Gabrilovich, D. (2004). Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nature Reviews, Immunology, 4, 941–952.

    Article  CAS  Google Scholar 

  160. Kusmartsev, S., & Gabrilovich, D. I. (2002). Immature myeloid cells and cancer-associated immune suppression. Cancer Immunology and Immunotherapy, 51, 293–298.

    Article  CAS  PubMed  Google Scholar 

  161. Serafini, P., De Santo, C., Marigo, I., Cingarlini, S., Dolcetti, L., Gallina, G., et al. (2004). Derangement of immune responses by myeloid suppressor cells. Cancer Immunology and Immunotherapy, 53, 64–72.

    Article  CAS  PubMed  Google Scholar 

  162. Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., et al. (2004). Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell, 6, 409–421.

    Article  CAS  PubMed  Google Scholar 

  163. Okazaki, T., Ebihara, S., Asada, M., Kanda, A., Sasaki, H., & Yamaya, M. (2006). Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models. International Immunology, 18, 1–9.

    Article  CAS  PubMed  Google Scholar 

  164. Ruiz de Almodovar, C., Luttun, A., & Carmeliet, P. (2006). An SDF-1 trap for myeloid cells stimulates angiogenesis. Cell, 124, 18–21.

    Article  CAS  PubMed  Google Scholar 

  165. Grunewald, M., Avraham, I., Dor, Y., Bachar-Lustig, E., Itin, A., Yung, S., et al. (2006). VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell, 124, 175–189.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel

    Ron N. Apte, Shahar Dotan, Moshe Elkabets, Malka R. White, Eli Reich, Yaron Carmi, Xiaping Song, Tatyana Dvozkin, Yakov Krelin & Elena Voronov

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  1. Ron N. Apte
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Apte, R.N., Dotan, S., Elkabets, M. et al. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev 25, 387–408 (2006). https://doi.org/10.1007/s10555-006-9004-4

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