GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment

Publication date: Available online 17 November 2018Source: Redox BiologyAuthor(s): Beth L. Worley, Yeon Soo Kim, Jennifer Mardini, Rameez Zaman, Kelly E. Leon, Piyushi Gupta Vallur, Asvelt Nduwumwami, Joshua I. Warrick, Patrick F. Timmins, Joshua P. Kesterson, Rébécca Phaëton, Nam Y. Lee, Vonn Walter, Lauren Endres, Karthikeyan Mythreye, Katherine M. Aird, Nadine HempelAbstractOvarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in the peritoneal cavity. At late stage abdominal cavity ascites accumulation provides a tumor-supporting medium in which cancer cells gain access to growth factors and cytokines that promote survival and metastasis. However, little is known about the redox status of ascites, or whether antioxidant enzymes are required to support ovarian cancer survival during transcoelomic metastasis in this medium. Gene expression cluster analysis of antioxidant enzymes identified two distinct populations of high-grade serous adenocarcinomas (HGSA), the most common ovarian cancer subtype, which specifically separated into clusters based on glutathione peroxidase 3 (GPx3) expression. High GPx3 expression was associated with poorer overall patient survival and increased tumor stage. GPx3 is an extracellular glutathione peroxidase with reported dichotomous roles in cancer. To further examine a potential pro-tumorigenic role of GPx3 in HGSA, stable OVCAR3 GPx3 knock-down cell...
Source: Redox Biology - Category: Biology Source Type: research