Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126
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Huai-Ching Tai1, An-Chen Chang2, Hong-Jeng Yu1, Chao-Yuan Huang1, Yu-Chieh Tsai3, Yu-Wei Lai4, Hui-Lung Sun5, Chih-Hsin Tang2,6,7 and Shih-Wei Wang8
1 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
2 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
3 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
4 Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan
5 Department of Molecular Virology, Immunology and Mediccal Genetics, Ohio state University, Columbus, OH, USA
6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
7 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
8 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
Shih-Wei Wang, email:
Chih-Hsin Tang, email:
Keywords: WISP-1; Osteoblasts; Prostate cancer; miR-126; VCAM-1
Received: May 29, 2014 Accepted: July 29, 2014 Published: July 30, 2014
Bone metastases of prostate cancer (PCa) may cause intractable pain. Wnt-induced secreted protein-1 (WISP-1) belongs to the CCN family (CTGF/CYR61/NOV) that plays a key role in bone formation. We found that osteoblast-conditioned medium (OBCM) stimulates migration and vascular cell adhesion molecule-1 (VCAM-1) expression in human PCa (PC3 and DU145) cells. Osteoblast transfection with WISP-1 shRNA reduced OBCM-mediated PCa migration and VCAM-1 expression. Stimulation of PCa with OBCM or WISP-1 elevated focal adhesion kinase (FAK) and p38 phosphorylation. Either FAK and p38 inhibitors or siRNA abolished osteoblast-derived WISP-1-induced migration and VCAM-1 expression. Osteoblast-derived WISP-1 inhibited miR-126 expression. Moreover, miR-216 mimic reversed the WISP-1-enhanced migration and VCAM-1 expression. This study suggests that osteoblast-derived WISP-1 promotes migration and VCAM-1 expression in human PCa cells by down-regulating miR-126 expression via αvβ1 integrin, FAK, and p38 signaling pathways. Thus, WISP-1 may be a new molecular therapeutic target in PCa bone metastasis.
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