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Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients

  1. Author:
    Yin, J.
    Yan, X. D.
    Yao, X.
    Zhang, Y. L.
    Shan, Y.
    Mao, N.
    Yang, Y. L.
    Pan, L. Y.
  2. Author Address

    [Yin, Jie; Yan, Xuedong; Yao, Xin; Zhang, Yongli; Shan, Ying; Pan, Lingya] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China. [Yin, Jie; Yan, Xuedong; Yao, Xin; Zhang, Yongli; Shan, Ying; Pan, Lingya] Peking Union Med Coll, Beijing 100730, Peoples R China. [Mao, Ning] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Cell Biol, Beijing 100730, Peoples R China. [Yang, Yili] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.;Pan, LY (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, 1 Shuai Fu Yuan,Wang Fu Jing St, Beijing 100730, Peoples R China;lingyapan@hotmail.com
    1. Year: 2012
    2. Date: Feb
  1. Journal: Journal of Cellular and Molecular Medicine
    1. 16
    2. 2
    3. Pages: 337-348
  2. Type of Article: Article
  3. ISSN: 1582-1838
  1. 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.

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External Sources

  1. DOI: 10.1111/j.1582-4934.2011.01316.x
  2. WOS: 000299633700013

Library Notes

  1. Fiscal Year: FY2011-2012
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