Abstract 805: Adaptation of mitochondrial organization to aggregation in serous ovarian cancer

Abstract

Abstract During metastasis, ovarian cancer cells exfoliate from the primary tumor and disseminate throughout the peritoneal cavity mostly as aggregates with a higher survival rate and metastatic potential. To determine how the mitochondrial morphology and dynamic expression of fusion and fission-regulating proteins contribute to spheroid survival, in this study we investigated changes in mitochondrial morphology in order to identify phenotypic alterations that are associated with changes in mitochondrial function. We compared monolayers and spheroids of murine and human benign, late-stage, and tumor-initiating cells in hypoxia using fluorescent microscopy and western blot analysis. In addition, we investigated how the mitochondrial membrane potential (Δψm) and ROS production contributed to this phenotype using the InCell analyzer with TMRM and Amplex Red dyes respectively. The data from this study suggest that the morphology and dynamic protein expression are highly altered during tumorigenesis, aggregation, and in hypoxic conditions, indicating a direct correlation of mitochondrial morphology in regulating survival, apoptosis and proliferation. The identification of these molecular events and changes that allow for the survival of metastatic cancer cells in an environment low in oxygen and nutrients may provide specific targets for interventions that would suppress successful metastatic outgrowth of disseminating cells and could potentially be used as a biomarker for treatment efficacy. Citation Format: Joseph P. Grieco, Stephanie Edwards, Mitchell Allen, Yao Wang, Justin Perry, Yipei Song, Nathan Swami, David Brown, Eva Schmelz. Adaptation of mitochondrial organization to aggregation in serous ovarian cancer [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 805.