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|標題:||Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin α4β1 system||作者:||Chang, An-Chen
|關鍵字:||ET-1;Integrin α4β1;Prostate cancer;VCAM-1;WISP-1;3T3 Cells;Animals;Bone Neoplasms;CCN Intercellular Signaling Proteins;Cell Adhesion;Cell Line, Tumor;Cell Movement;Coculture Techniques;Culture Media, Conditioned;Endothelin-1;Gene Expression Regulation, Neoplastic;Humans;Integrin alpha4beta1;Male;Mice;Neoplasm Transplantation;Osteoblasts;Osteogenesis;Prostatic Neoplasms;Proto-Oncogene Proteins;RAW 264.7 Cells;Signal Transduction;Vascular Cell Adhesion Molecule-1||Project:||Cancer letters, Volume 426, Page(s) 47-56.||摘要:||
Bone metastasis is a frequent occurrence in prostate cancer (PCa) that is associated with severe complications such as fracture, bone pain and hypercalcemia. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. In our previous data, we have described how the involvement of the Wnt-induced secreted protein-1/vascular cell adhesion molecule-1 (WISP-1/VCAM-1) system in this tumor-bone interaction contributes to human PCa cell motility. In this study, we found that WISP-1 regulates bone mineralization by inducing bone morphogenetic protein-2 (BMP2), BMP4 and osteopontin (OPN) expression in osteoblasts. We also found that WISP-1 inhibited RANKL-dependent osteoclastogenesis. Moreover, osteoblast-derived WISP-1 enhanced VCAM-1 expression in PCa cells and subsequently promoted the adherence of cancer cells to osteoblasts. Furthermore, endothelin-1 (ET-1) expression in PCa cells was regulated by osteoblast-derived WISP-1, which promoted integrin α4β1 expression in osteoblasts via the MAPK pathway. Pretreatment of PCa cells with VCAM-1 antibody or osteoblasts with integrin α4β1 antibody attenuated the adherence of PCa cells to osteoblasts, suggesting that integrin α4β1 serves as a ligand that captures VCAM-1+ metastatic tumor cells adhering to osteoblasts. Our findings reveal that osteoblast-derived WISP-1 plays a key role in regulating the adhesion of PCa cells to osteoblasts via the VCAM-1/integrin α4β1 system. Osteoblast-derived WISP-1 is a promising target for the prevention and inhibition of PCa-bone interaction.
|Appears in Collections:||生物醫學研究所|
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