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

Research output: Contribution to journalArticle

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
JournalOncogene
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Gelsolin
Exosomes
Ovarian Neoplasms
Recurrence
Survival
Cisplatin
Actins
Neoplasms
Cell Survival
Protein Isoforms
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Asare-Werehene, M., Nakka, K., Reunov, A., Chiu, C. T., Lee, W. T., Abedini, M. R., ... Tsang, B. K. (Accepted/In press). The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance. Oncogene. https://doi.org/10.1038/s41388-019-1087-9
Asare-Werehene, Meshach ; Nakka, Kiran ; Reunov, Arkadiy ; Chiu, Chen Tzu ; Lee, Wei Ting ; Abedini, Mohammad R. ; Wang, Pei Wen ; Shieh, Dar Bin ; Dilworth, F. Jeffrey ; Carmona, Euridice ; Le, Tien ; Mes-Masson, Anne Marie ; Burger, Dylan ; Tsang, Benjamin K. / The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance. In: Oncogene. 2019.
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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.",
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Asare-Werehene, M, Nakka, K, Reunov, A, Chiu, CT, Lee, WT, Abedini, MR, Wang, PW, Shieh, DB, Dilworth, FJ, Carmona, E, Le, T, Mes-Masson, AM, Burger, D & Tsang, BK 2019, 'The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance', Oncogene. https://doi.org/10.1038/s41388-019-1087-9

The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance. / Asare-Werehene, Meshach; Nakka, Kiran; Reunov, Arkadiy; Chiu, Chen Tzu; Lee, Wei Ting; Abedini, Mohammad R.; Wang, Pei Wen; Shieh, Dar Bin; Dilworth, F. Jeffrey; Carmona, Euridice; Le, Tien; Mes-Masson, Anne Marie; Burger, Dylan; Tsang, Benjamin K.

In: Oncogene, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance

AU - Asare-Werehene, Meshach

AU - Nakka, Kiran

AU - Reunov, Arkadiy

AU - Chiu, Chen Tzu

AU - Lee, Wei Ting

AU - Abedini, Mohammad R.

AU - Wang, Pei Wen

AU - Shieh, Dar Bin

AU - Dilworth, F. Jeffrey

AU - Carmona, Euridice

AU - Le, Tien

AU - Mes-Masson, Anne Marie

AU - Burger, Dylan

AU - Tsang, Benjamin K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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