Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer.

Abstract

Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion: MFN1/OPA1, fission: DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.

• Authors: Joseph P Grieco, Mitchell E Allen, Justin B Perry, Yao Wang, Yipei Song, Ali Rohani, Stephanie L E Compton, James W Smyth, Nathan S Swami, David A Brown, Eva M Schmelz
• Journal: Frontiers in oncology (Front Oncol) Vol. 10 Pg. 600113 ( 2020) ISSN: 2234-943X [Print] Switzerland
• PMID: 33520711 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Grieco, Allen, Perry, Wang, Song, Rohani, Compton, Smyth, Swami, Brown and Schmelz.