Oncotarget

Research Papers:

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

Chun-Chi Chen, Shiow-Her Chiou, Cheng-Lin Yang, Kuan-Chih Chow _, Tze-Yi Lin, Hui-Wen Chang, Weir-Chiang You, Hisu-Wen Huang, Chien-Min Chen, Nien-Cheng Chen, Fen-Pi Chou and Ming-Chih Chou

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Oncotarget. 2017; 8:77152-77167. https://doi.org/10.18632/oncotarget.20414

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Abstract

Chun-Chi Chen1,2, Shiow-Her Chiou3, Cheng-Lin Yang4, Kuan-Chih Chow4, Tze-Yi Lin5, Hui-Wen Chang5, Weir-Chiang You6, Hisu-Wen Huang7, Chien-Min Chen7, Nien-Cheng Chen8, Fen-Pi Chou8 and Ming-Chih Chou1,9

1Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan

2Section of Urology, Department of Surgery, Changhua Christian Hospital, Chang-Hua, Taiwan

3Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taichung, Taiwan

4Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan

5Department of Pathology, China Medical University Hospital, China Medical University, Taichung, Taiwan

6Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan

7Endemic Species Research Institute, Council of Agriculture, Executive Yuan, Chi-Chi, Taiwan

8Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan

9Department of Family and Community Medicine, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan

Correspondence to:

Kuan-Chih Chow, email: [email protected]

Ming-Chih Chou, email: [email protected]

Keywords: prostate cancer, gelsolin, sortilin, CD37, tumor-infiltrated lymphocytes

Received: January 13, 2017    Accepted: June 12, 2017    Published: August 23, 2017

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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