The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance

Meshach Asare-Werehene, Kiran Nakka, Arkadiy Reunov, Chen Tzu Chiu, Wei Ting Lee, Mohammad R. Abedini, Pei Wen Wang, Dar Bin Shieh, F. Jeffrey Dilworth, Euridice Carmona, Tien Le, Anne Marie Mes-Masson, Dylan Burger, Benjamin K. Tsang

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2 Citations (Scopus)

Abstract

Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of the actin-associated protein cytosolic gelsolin (GSN) regulates the gynecological cancer cell fate resulting in dysregulation in chemosensitivity. In this study, we report that elevated expression of plasma gelsolin (pGSN), a secreted isoform of GSN and expressed from the same GSN gene, correlates with poorer overall survival and relapse-free survival in patients with OVCA. In addition, it is highly expressed and secreted in chemoresistant OVCA cells than its chemosensitive counterparts. pGSN, secreted and transported via exosomes (Ex-pGSN), upregulates HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as confers cisplatin resistance in otherwise chemosensitive OVCA cells. These findings support our hypothesis that exosomal pGSN promotes OVCA cell survival through both autocrine and paracrine mechanisms that transform chemosensitive cells to resistant counterparts. Specifically, pGSN transported via exosomes is a determinant of chemoresistance in OVCA.

Original languageEnglish
Pages (from-to)1600-1616
Number of pages17
JournalOncogene
Volume39
Issue number7
DOIs
Publication statusPublished - 2020 Feb 13

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Asare-Werehene, M., Nakka, K., Reunov, A., Chiu, C. T., Lee, W. T., Abedini, M. R., Wang, P. W., Shieh, D. B., Dilworth, F. J., Carmona, E., Le, T., Mes-Masson, A. M., Burger, D., & Tsang, B. K. (2020). The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance. Oncogene, 39(7), 1600-1616. https://doi.org/10.1038/s41388-019-1087-9