Abstract
Malignant tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign tissue and in high-grade epithelial ovarian carcinoma (EOC) in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n = 1435) showed that gene expression of specific mitochondrial proteins in EOC is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in tissue from 51 patients with benign ovarian masses and 128 patients with high-grade EOC revealed that compared to benign tissue, EOCs exhibit 3.3–8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P < 0.001) but similar mitochondrial DNA (mtDNA) levels (− 3.1%), documenting abnormal mitochondrial phenotypes in EOC. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r = − 0.43 to 0.47). In contrast, serous EOCs showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in EOC and warrant further research on the link between biobehavioral factors and mitochondria in cancer.
Highlights
Malignant tumor cells exhibit mitochondrial alterations and are influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored
To explore whether mitochondrial remodeling represents a potential pathway by which biobehavioral processes may support tumor growth and progression, we quantified the association of biobehavioral factors and mitochondrial phenotypes in epithelial ovarian carcinomas (EOC) or benign tissue
Among 614 women with ovarian cancer cases followed over 20 years, we found that relative to those with high MPC2 gene expression, low MPC expression was associated with a 59% increase in mortality (p < 0.0001, Fig. 1A), suggesting that mitochondrial metabolism contributes to ovarian tumor biology in humans
Summary
Malignant tumor cells exhibit mitochondrial alterations and are influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Mitochondria have been shown to dynamically respond to biobehavioral processes and to be functionally linked to the major neuroendocrine and immune pathways that are known to be modulated by psychological states[17,18,19] This includes glucocorticoid stress hormones released during psychosocial stress and their associated metabolic effects[20]. Both the respiratory chain involved in energy production and macromolecule biosynthesis, as well as the maintenance of the mitochondrial genome, can be a target of biobehavioral processes Considering both these genetic and biochemical aspects, we recently developed a high-throughput approach to simultaneously monitor i) mitochondrial content and ii) functional capacity in human blood leukocytes[22]. Acute mental stress that induces negative mood can lead to the release of the potentially immunogenic circulating cell-free mtDNA (cf-mtDNA) in plasma and serum within minutes 23,24, providing further evidence that mitochondria in normal (i.e., non-cancerous) tissues functionally respond to biobehavioral factors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
