Fibroblasts in Ovarian Cancer

Fibroblasts are cells responsible for synthesizing the stroma of animal tissue including the extracellular matrix and collagen.  In cancer, these cells can be reprogrammed to aid in tumor growth and progression. In the cancer associated fibroblasts (CAFs) of epithelial ovarian cancer, miR-31 and miR-214 were downregulated, while miR-155 was upregulated (Mitra et al 2012).  The authors also found that mimicking this induced a functional conversion of normal fibroblasts into CAFs, and reversal caused reversion of CAFs to normal fibroblasts. When miR-214 is downregulated in CAFs, the CAFs secrete high levels of the chemokine CCL5 into the tumor microenvironment.  The authors found that miR-214 is a target of CCL5. Therefore, due to the downregulation of miR-214 in CAFs, it can no longer silence the CCL5 mRNA, so it gets translated at a much higher level. CCL5 secreted by CAFs is known to be a tumor promoting factor. It is higher and involved in cisplatin resistance because it is secreted from the CAFs and signals through STAT3/PI3K/AKT on ovarian cancer cells.