title: Osteoblast-derived WNT-induced secreted protein 1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126.
abstract: Bone metastases of prostate cancer (PCa) may cause intractable pain. Wnt-1-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 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.
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Huai-Ching
authors.initials: HC
authors.lastname: Tai
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: An-Chen
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hong-Jeng
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Lai
authors.affiliation: Department of Molecular Virology, Immunology and Mediccal Genetics, Ohio state University, Columbus, OH, USA.
authors.forename: Hui-Lung
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1