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Identification of CD109 in the extracellular vesicles derived from ovarian cancer stem-like cells
Ye Eun Kim 1,# (Research worker), Jun Se Kim 2,# (Graduate student), Min Joo Shin2 (Graduate student), Seo Yul Lee 2 (Graduate student), Dae Kyoung Kim1 (Research worker), Nam-Kyung Lee3 (Research worker), Yang Woo Kwon4 (Research worker), Kyung-Un Choi5 (Professor), Dong-Soo Suh 6 (Professor), Byoung Soo Kim7 (Professor), Sanghwa Jeong7 (Professor), Jae Ho Kim 1,2,* (Professor)
1Hicelltech Inc.,
2Department of Physiology, School of Medicine, Pusan National University,
3Biotherapeutics Translational Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB),
4New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub),
5Department of Pathology and 6Department of Obstetrics and Gynecology, School of Medicine, Pusan National University,
7School of Biomedical Convergence Engineering, Pusan National University
Abstract
Ovarian cancer is the deadliest gynecological cancer because it has few early symptoms and metastasizes to the surrounding organs at advanced stages. Cancer stem cells (CSCs), a subpopulation of cells with acquired drug resistance, contribute to the recurrence and poor prognosis of ovarian cancer. CD109, a cell surface glycoprotein, has been reported to be a marker of CSCs; however, it remains unclear whether CD109 is secreted by CSCs. In this study, we investigated the amount of CD109 in conditioned media (CM) of CSC populations from ovarian cancer cell lines and patients with ovarian cancer. The CM of sphere-forming CSCs isolated from ovarian cancer cell lines (A2780 and SKOV3) had higher levels of CD109 than those isolated from their adherent cultured parental cells. Furthermore, higher levels of CD109 were detected on the cell surface and in the CM of sphere-forming CSC populations isolated from patient-derived primary ovarian cancer cells. To clarify whether CD109 is localized to the exosomal fraction secreted from CSCs, extracellular vesicles were isolated from the CM by ultracentrifugation. In addition to the CM, the exosomal fraction of ovarian CSCs contained greater levels of CD109 than the parental cells. These results suggest that CD109 is secreted in a soluble or exosomal form from CSCs, and that the measurement of secreted CD109 may be used as a diagnostic or prognostic marker for ovarian cancer.
Abstract, Accepted Manuscript [Submitted on January 15, 2024, Accepted on April 8, 2024]
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