Author:
Charoenkwan Kittipat,Apaijai Nattayaporn,Sriwichaiin Sirawit,Chattipakorn Nipon,Chattipakorn Siriporn C.
Abstract
AbstractMetabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.
Funder
Thailand Research Fund
Chiang Mai University
National Science and Technology Development Agency
National Research Council of Thailand
Publisher
Springer Science and Business Media LLC
Reference30 articles.
1. Fleming, G., Seidman, J. & Lengyel, E. Principles and practice of gynecologic oncology 757–847 (Lippincott Williams & Wilkins, 2013).
2. Kong, C. S., Longacre, T. A. & Hendrickson, M. R. Berek & Hacker’s gynecologic oncology 123–219 (Wolters Kluwer, 2015).
3. Suh, D. H., Kim, M. K., No, J. H., Chung, H. H. & Song, Y. S. Metabolic approaches to overcoming chemoresistance in ovarian cancer. Ann. N. Y. Acad. Sci. 1229, 53–60. https://doi.org/10.1111/j.1749-6632.2011.06095.x (2011).
4. Liu, V. W. et al. High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer. Res. 61, 5998–6001 (2001).
5. Permuth-Wey, J. et al. Inherited variants in mitochondrial biogenesis genes may influence epithelial ovarian cancer risk. Cancer Epidemiol. Biomark. Prev. 20, 1131–1145. https://doi.org/10.1158/1055-9965.EPI-10-1224 (2011).