Abstract 1883: Ovarian cancer cells overcome the cytotoxic effect of cisplatin by hyper activating CCR9-mediated signaling in response to cisplatin

Abstract

Abstract Ovarian cancer (OC) has highest mortality rate among the gynecological malignancies. Chemotherapies, in combination with surgery, are standard treatment offered to the patients with advanced OC. Although 80% patients initially respond to platinum-based chemotherapy, clinical responses remain short-lived due to chemoresistance. Most patients experience relapse and 50-60% of them die within 5 years. Therefore, development of novel therapies for OC remains a high priority. Hence, the major focus of this study is to define the biology of CCR9, which is highly expressed in OC in response to platinum drug. Effect of cisplatin on CCR9 expression and impact of CCR9 activation on molecular and cellular changes involved in overcoming the effect of cisplatin was determined by flow cytometric and western blot analyses. Our data show higher expression of CCR9 and CCL25 in OC cells in response to cisplatin treatment. Additionally, our data show higher expression and activation of estrogen receptor-α (ER- α) in OC cell after CCR9 activation. In addition to this, we show CCR9-mediated expression of Smoothened (SMO) known to support stem cell like phenotype by activating Hedgehog signaling and co-expression of CD44 and CCR9 as well as higher CD44 expression in OC cells following CCL25 treatment. CCR9-CCL25 axis promoted epithelial to mesenchymal transition. These observations strongly show an association of CCR9-CCL25 axis in OC pathogenesis, therapeutic resistance, and chemotherapeutic efficacy. Citation Format: Hina Mir, Neeraj Kapur, Shailesh Singh. Ovarian cancer cells overcome the cytotoxic effect of cisplatin by hyper activating CCR9-mediated signaling in response to cisplatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1883.