Daniela Matei, MD
Atransglutaminase 2 Modulates Sensitivity to Chemotherapy in Ovarian Cancer
The most significant cause of death and illness related to ovarian cancer is its propensity to spread in the abdomen. However, the mechanisms responsible for spread are not known. We discovered that an enzyme called transglutaminase 2 (TG2) is present at high levels in ovarian tumors, in abdominal fluid recovered from patients with cancer and in ovarian cancer cells. We also found that this protein facilitates the spreading and adhesion of ovarian cancer cells to the extra-cellular matrix by modulating the function of beta integrins. We hypothesized by modulating tumor cell interaction with the microenvironment TG2 regulates the process of intra-peritoneal metastasis and the response to chemotherapy. In this proposal we will evaluate the physical and functional interaction between TG2 and integrins in ovarian cancer cells and tumors. This interaction may ultimately alter the way ovarian cancer cells respond to chemotherapy. If TG2 alters sensitivity to chemotherapy, the next step will be to test inhibitors of TG2 in conjunction with chemotherapy.