Presentation description

Post-menopausal breast cancer risk and mortality rates are exacerbated by those who are classified as obese, such that a 5-unit increase in body mass index is linked to a 12% increase in risk. The rising rates of obesity make understanding the link between obesity and the incidence, progression, and mortality of breast cancer of high priority. Among the numerous reasons why obesity exacerbates breast cancer, the innate role of the lean adipose tissue has gone unrecognized.

We found lean adipocytes inhibit breast cancer cell growth by releasing the paracrine factor 9S-HODE, a polyunsaturated lipid, which can interact with iron to induce a specific type of cell death known as ferroptosis. We know obese adipocytes produce less 9S-HODE than lean adipocytes. Further, our preliminary data suggests that non-cancer cells are less sensitive to lean adipocyte-secreted 9S-HODE, and we have shown that 9S-HODE can cause ferroptosis in breast cancer cells. Therefore, we hypothesize that non-cancer cells are less sensitive to ferroptosis. We will test this by treating both cancer cells and epithelial cells with varying concentrations of ferroptosis-inducing drugs to gauge sensitivity.

Additionally, we found that breast cancer cell lines affected by lean adipocytes undergo ferroptosis in vitro. Therefore, we hypothesize tumors from lean mice will also undergo ferroptosis in vivo. We will measure if these tumors produce 4-HNE, a product of ferroptosis, through western blots, and will compare the amount of 4-HNE present in tumors grown in lean adipose tissue than in obese tissue. Understanding the role of ferroptosis in breast cancer cells, specifically in the context of obesity, is beneficial to understanding why obesity is correlated with higher incidences of breast cancer and for developing a cancer treatment that could induce cell death in cancer cells while leaving healthy body tissue alive.