title: Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients.
abstract: Early detection of resistance to platinum-based therapy is critical for improving the treatment of ovarian cancers. We have previously found that increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer cells. Here we demonstrate that annexin A3 can be detected in the culture medium of ovarian cancer cells, particularly these cells that express high levels of annexin A3. Levels of annexin A3 were then determined in sera from ovarian cancer patients using an enzyme-linked immunosorbent assay. Compared with those from normal donors, sera from ovarian cancer patients contain significantly higher levels of annexin A3. Furthermore, serum levels of annexin A3 were significantly higher in platinum-resistant patients than in platinum-sensitive patients. To gain insight into the mechanism of secretion, the ovarian cancer cell lines were examined using both transmission electron microscopy and immunoelectron microscopy. Compared with parent cells, there are significantly more vesicles in the cytoplasm of ovarian cancer cells that express high levels of annexin A3, and at least some vesicles are annexin A3-positive. Moreover, some vesicles appear to be fused with the cell membrane, suggesting that annexin A3 secretion may be associated with exocytosis and the release of exosomes. This is supported by our observation that ovarian cancer cells expressing higher levels of annexin A3 released increased numbers of exosomes. Furthermore, annexin A3 can be detected in exosomes released from cisplatin-resistant cells (SKOV3/Cis) by immunoblotting and immunoelectron microscopy.
authors: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Jie
authors: J
authors: Yin
authors: Xuedong
authors: X
authors: Yan
authors: Xin
authors: X
authors: Yao
authors: Yongli
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: Shan
authors: Ning
authors: N
authors: Mao
authors: Yili
authors: Y
authors: Yang
authors: Lingya
authors: L
authors: Pan
mesh_terms: D000368:Aged; D017318:Annexin A3 / Q000097:blood* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D019008:Drug Resistance, Neoplasm; D005089:Exocytosis / Q000502:physiology; D055354:Exosomes / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010984:Platinum / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D010984:Platinum; D017318:Annexin A3