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Corticotropin-releasing factor family and its receptors: Tumor therapeutic targets?

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Abstract

Urocortin (UCN) and corticotropin-releasing factor (CRF) are members of CRF family. Though CRF is mainly distributed in central nervous system (CNS), UCN has been reported to play biologically diverse roles in several systems such as cardiovascular, respiratory, digestive, reproductive, stress, immunologic system, etc. UCN and CRF bind to two known receptors, CRFR1 and CRFR2, to function. Both CRF receptors are distributed in CNS and periphery tissues, and their expression in cancer tissues has been reported. Now there are many documents indicating UCN/CRF play an important role in the regulation of carcinogenesis. There is also evidence indicating UCN/CRF have anticancer effects via CRFRs. This paper will review the effects of CRF family in cancers.

Section snippets

Possible role of CRFR1 in tumor

There are many documents indicating that CRFR1 was expressed in tumor cells and UCN/CRF could inhibit tumor cell growth via CRFR1 [14], [15], [16], [17], [18], [19]. It was showed that human neuroblastoma SH-SY5Y cells mainly expressed CRFR1 which was functionally coupled with cAMP formation [14]. Graziani et al. reported that UCN/CRF inhibited the growth of adenocarcinoma ishikawa cells time- and concentration-dependently, and this effect was mediated by CRFR1 [15]. It was also reported that

Role of CRFR2 in tumor angiogenesis

Though there are few reports about CRFR2 and tumors, the role of CRFR2 in tumoral formation and angiogenesis is being more and more followed with interest. Florio et al. found that UCN-mRNA was significantly reduced in human endometrial carcinoma versus healthy controls, and UCN peptide was not found in neopalstic samples [12]. Though CRF/UCN were reported to inhibit endometrium carcinoma cells via CRFR1 [15], the authors did not exclude CRFR2 involvement in tumor procession [12]. These

Other beneficial effects of UCN in tumor chemotherapy

Currently, cancer therapy drugs are aiming to multiple mechanisms of the generation and development of cancers. The effects of UCN on these aspects are gradually recognized.

It is widely accepted that cytotoxic agents have many severe side effects as traditional cytotoxic agents against cancer, such as chemotherapy-induced nausea and vomiting (CINV), cardiotoxicity, nephrotoxicity, myelosuppression, etc. As well known, most chemotherapeutic agents can injure gastrointestinal tract mucosa, and

Conclusion

UCN and CRF can directly inhibit tumor cell growth via CRFR1. Moreover, they can be recognized as biological response modifiers in cancer therapy. UCN can inhibit tumor angiogenesis via CRFR2, may reduce side effects of cytotoxic agents and enhance the curative effects of chemotherapeutics. Furthermore, UCN might be a potential MDR reversal agent.

Acknowledgment

This work was supported by Key Project of Jiangsu Provincial Natural Scientific Fund (BK2006727).

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