Ovarian cancer most frequently metastasizes to the omentum, a major site of intra-abdominal fat in post-menopausal women. This proposal seeks to characterize how the omental adipocytes (fat cells) and fibroblasts (support cells) recruit ovarian tumor cells to the omentum and facilitate the spread of this deadly disease. Our preliminary data suggest that specific, two-way communication occurs between ovarian cancer cells and omental fat and fibroblast cells that not only promotes tumor growth and metastasis in the omentum, but also confers chemoresistance to the tumor cells. We have identified a regulatory molecule, miR-21, that is transferred specifically from omental to ovarian tumor cells. We speculate miR-21 plays an important role in promoting the aggressive behavior of metastatic ovarian cancer, and will characterize its effects on the ability of ovarian cancer cells to invade other tissues and resist the effects of chemotherapy.
The identification of direct mechanisms of communication between omental cells and tumor cells, which promote aggressive tumor behavior, suggests that the development of drugs that interrupt this intracellular communication may prove clinically useful as a strategy to prevent ovarian tumor progression and improve outcomes for obese cancer patients.