Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

Oncotarget
Chun-Chi ChenMing-Chih Chou

Abstract

Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. In vitro, secreted gelsolin inactivated CD4(+) T cells by binding to CD37, and induced apoptosis of activated CD8(+) T lymphocytes by binding to Fas ligand during cell contact dependent on major histocompatibility complex I. Moreover, secreted gelsolin bound to sortilin, which in turn bound to Wiskott-Aldrich syndrome protein family member 3, thereby enhancing the endocytosis and intracellular transport of essential lipids needed to facilitate tumor growth and expansion. Under normal conditions, gelsolin is a seemingly harmless protein that prevents immune responses in female recipients. In disease states, however, this protein can inhibit immunosurveillance and promote cancer progression.

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Citations

Sep 29, 2019·Scientific Reports·Meshach Asare-WereheneBenjamin K Tsang
Jun 4, 2021·Cell·Evangelos GiampazoliasCaetano Reis e Sousa
Jun 20, 2021·Brazilian Journal of Otorhinolaryngology·Akın ŞahinAbdullah Çağlar Batman
Sep 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sayantan JanaZamaneh Kassiri

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Datasets Mentioned

BETA
AK315494

Methods Mentioned

BETA
bone marrow section
enzyme-linked immunosorbent assay
immunoprecipitation
nuclear translocation
electrophoresis
transfection
flow cytometry
dissection

Software Mentioned

MS
fit
ASW
GraphPad
Adobe Photoshop
GraphPad Prism6
CXP
FV10

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