Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

COL6A3 Exosomes Promoting Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer

Version 1 : Received: 18 June 2024 / Approved: 18 June 2024 / Online: 18 June 2024 (11:51:32 CEST)

A peer-reviewed article of this Preprint also exists.

Ho, C.-M.; Yen, T.-L.; Chang, T.-H.; Huang, S.-H. COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer. Int. J. Mol. Sci. 2024, 25, 8121. Ho, C.-M.; Yen, T.-L.; Chang, T.-H.; Huang, S.-H. COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer. Int. J. Mol. Sci. 2024, 25, 8121.

Abstract

Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival in EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, P <0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibit reduced invasion ability (p<0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p<0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p=0.007) or SKOV3/COL6A3 cells and PBS (p=0.039). Knockdown of COL6A3 or treatment with EXs inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness in EOC.

Keywords

exosomes; COL6A3; metastasis; epithelial ovarian cancer; aggressiveness; exosomes inhibitor

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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