Fibroblasts present in the stroma of ovarian cancer cells can be programmed to become cancer-associated fibroblasts by changing the expression pattern of three microRNAs (miRNAs), according to a study published online Nov. 21 in Cancer Discovery.
Anirban K. Mitra, Ph.D., from the University of Chicago, and colleagues compared miRNA expression in cancer-associated fibroblasts from patients with ovarian cancer and normal or tumor-adjacent fibroblasts.
The researchers found that two miRNAs were downregulated (miR-31 and miR-214) and one was upregulated (miR-155) in cancer-associated fibroblasts. Replicating this pattern of expression in normal fibroblasts converted them into cancer-associated fibroblasts, while correcting this expression pattern in cancer-associated fibroblasts converted them into normal fibroblasts. Cancer-associated fibroblasts had increased expression of chemokines known to be important for their function, particularly the chemokine C-C motif ligand 5, which was a direct target of miR-214.
“These results indicate that ovarian cancer cells reprogram fibroblasts to become cancer-associated fibroblasts though the action of miRNAs,” Mitra and colleagues conclude. “Targeting these miRNAs in stromal cells could have therapeutic benefit.”