Nocquet Lisa, Juin Philippe P, Souazé Frédérique
Inserm, CRCINA, Université de Nantes, F-44000 Nantes, France.
Cancers (Basel). 2020 Oct 17;12(10):3017. doi: 10.3390/cancers12103017.
Resistance of solid cancer cells to chemotherapies and targeted therapies is not only due to the mutational status of cancer cells but also to the concurring of stromal cells of the tumor ecosystem, such as immune cells, vasculature and cancer-associated fibroblasts (CAFs). The reciprocal education of cancer cells and CAFs favors tumor growth, survival and invasion. Mitochondrial function control, including the regulation of mitochondrial metabolism, oxidative stress and apoptotic stress are crucial for these different tumor progression steps. In this review, we focus on how CAFs participate in cancer progression by modulating cancer cells metabolic functions and mitochondrial apoptosis. We emphasize that mitochondria from CAFs influence their activation status and pro-tumoral effects. We thus advocate that understanding mitochondria-mediated tumor-stroma interactions provides the possibility to consider cancer therapies that improve current treatments by targeting these interactions or mitochondria directly in tumor and/or stromal cells.
实体癌细胞对化疗和靶向治疗的耐药性不仅归因于癌细胞的突变状态，还归因于肿瘤生态系统中基质细胞的协同作用，如免疫细胞、脉管系统和癌症相关成纤维细胞（CAFs）。癌细胞与CAFs之间的相互作用促进了肿瘤的生长、存活和侵袭。线粒体功能控制，包括线粒体代谢、氧化应激和凋亡应激的调节，对于这些不同的肿瘤进展步骤至关重要。在本综述中，我们重点关注CAFs如何通过调节癌细胞的代谢功能和线粒体凋亡来参与癌症进展。我们强调，CAFs的线粒体影响其激活状态和促肿瘤作用。因此，我们主张，了解线粒体介导的肿瘤-基质相互作用为考虑癌症治疗提供了可能性，即通过靶向这些相互作用或直接针对肿瘤和/或基质细胞中的线粒体来改进当前的治疗方法。
