Elsevier

Translational Research

Volume 209, July 2019, Pages 55-67
Translational Research

The double edge sword of fibrosis in cancer

https://doi.org/10.1016/j.trsl.2019.02.006Get rights and content
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Cancer-associated fibrosis is a critical component of the tumor microenvironment (TME) which significantly impacts cancer behavior. However, there is significant controversy regarding fibrosis as a predominantly tumor promoting or tumor suppressing factor. Cells essential to the generation of tissue fibrosis such as fibroblasts and mesenchymal stem cells (MSCs) have dual phenotypes dependent upon their independence or association with cancer cells. Cancer-associated fibroblasts and cancer-associated MSCs have unique molecular profiles which facilitate cancer cell cross talk, influence extracellular matrix deposition, and direct the immune system to generate a protumorigenic environment. In contrast, normal tissue fibroblasts and MSCs are important in restraining cancer initiation, influencing epithelial cell differentiation, and limiting cancer cell invasion. We propose this apparent dichotomy of function is due to (1) cancer mediated stromal reprogramming; (2) tissue stromal source; (3) unique subtypes of fibrosis; and (4) the impact of fibrosis on other TME elements. First, as cancer progresses, tumor cells influence their surrounding stroma to move from a cancer restraining phenotype into a cancer supportive role. Second, cancer has specific organ tropism, thus stroma derived from preferred metastatic organs support growth while less preferred metastatic tissues do not. Third, there are subtypes of fibrosis which have unique function to support or inhibit cancer growth. Fourth, depleting fibrosis influences other TME components which drive the cancer response. Collectively, this review highlights the complexity of cancer-associated fibrosis and supports a dual function of fibrosis which evolves during the continuum of cancer growth.

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