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Abstract
Introduction/Background Recent studies have shown that the research of tumor cells alone cannot explain many phenomena in tumors, so the concept of tumor microenvironment has attracted more and more attention in tumor research. Studies have found that tumor cells need to interact with other cells, especially cancer associated fibroblasts (CAFs) to promote tumor progression. COL5A2 belongs to collagen family and is an important part of extracellular matrix in tumor microenvironment. Therefore, taking COL5A2 as the core to clarify the specific mechanism of the interaction between ovarian cancer cells and CAFs in the ovarian tumor microenvironment can provide a theoretical basis for the development of new treatment strategies for ovarian cancer.
Methodology We analyzed the expression of COL5A2 in 65 cases of ovarian cancer tissue specimens and explored the mechanism of altered COL5A2 expression in ovarian tumor microenvironment. Then we explored the underlying mechanisms of the effect of COL5A2 on cell proliferation, migration and invasion of ovarian cancer in vitro and in vivo.
Results (1) Compared with normal ovarian tissues, COL5A2 is highly expressed in ovarian cancer tissues, and when COL5A2 is highly expressed, the prognosis of ovarian cancer is worse.(2) COL5A2 mainly comes from CAFs.(3) The exosomes carrying ITGB1 secreted by ovarian cancer cells can activate the function of CAFs and promote the expression and secretion of COL5A2.(4) COL5A2 can activate FAK/PI3K/AKT signaling pathway of ovarian cancer cells by combining with ITGAV on the surface of ovarian cancer cells, thus promoting the proliferation, migration and invasion of ovarian cancer.
Conclusion Ovarian cancer cells activate CAFs and promote their expression and secretion of COL5A2 by secreting exosomes carrying ITGB1. COL5A2, which is widely expressed and secreted, can act as the signal molecule feedback on ovarian cancer cells to promote the proliferation, migration and invasion of ovarian cancer.