KEY TAKEAWAYS
- The study aimed to investigate the role of omental adipocyte-derived exosomes in promoting EOC invasion and resistance to paclitaxel chemotherapy.
- Researchers noticed that omental adipocytes foster a tumor-friendly and chemoresistant environment in OC.
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, with high mortality rates often attributed to chemotherapy resistance. EOC frequently invades the omentum, a fatty organ in the peritoneum, where omental adipocytes may play a role in disease progression, metastasis, and resistance to treatment. The underlying signaling mechanisms driving EOC’s preference for the omentum are not well understood.
Michael Ellis Williams and his team aimed to explore how exosomes derived from omental adipocytes influence EOC invasion and resistance to paclitaxel chemotherapy.
They performed an inclusive analysis using 3-dimensional co-culture models to investigate interactions between adipocytes and EOC. They assessed the effects of adipocytes on EOC proliferation, therapeutic response, and invasive capacity.
The primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were extracted from conditioned media of omentum tissue, and their impact on EOC was evaluated. Exosomal microRNA (miRNA) sequencing identified miRNAs prevalent in omental exosomes, and EOC cells were transfected with highly abundant miRNAs, including miR-21, let-7b, miR-16, and miR-92a.
The capacity of adipocytes to induce an invasive phenotype in patients with EOC, researchers demonstrated that this effect is mediated through the promotion of epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue from patients with OC and those without malignancies were found to induce proliferation, upregulate EMT markers, and decrease response to paclitaxel therapy in EOC cell lines and patient samples of HGSOC.
The analysis of exosomes derived from the omentum of cancer patients revealed highly abundant miRNAs, including miR-21, let-7b, miR-16, and miR-92a, which promoted cancer cell proliferation and conferred protection from chemotherapy when transfected into OC cells.
The study concluded that omental adipocytes can create a pro-tumorigenic and chemoprotective microenvironment in OC and other malignancies associated with adipose tissue.
The study was funded by Health Care Research Wales (HCRW), the Medical Research Council UK Confidence in Concept grant (MC_PC_19053), the Medical Research Council UK Impact Acceleration Account grant (MR/X502686/1). Welsh Government ERDF SMART Expertise 2014–2022 West Wales and the Valleys grants (2017/COL/001 and 2017/COL/004), and Swansea University Texas academic partnership PhD programme.
Source: https://pubmed.ncbi.nlm.nih.gov/39285292/
Williams ME, Howard D, Donnelly C, et al. (2024). “Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.” Cell Commun Signal. 2024;22(1):443. Published 2024 Sep 16. doi:10.1186/s12964-024-01806-4
