Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin α4β1 system.

Abstract

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.

• Authors: An-Chen Chang, Po-Chun Chen, Yu-Feng Lin, Chen-Ming Su, Ju-Fang Liu, Tien-Huang Lin, Show-Mei Chuang, Chih-Hsin Tang
• Journal: Cancer letters (Cancer Lett) Vol. 426 Pg. 47-56 (07 10 2018) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 29627497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• CCN Intercellular Signaling Proteins
• CCN4 protein, human
• Culture Media, Conditioned
• Endothelin-1
• Integrin alpha4beta1
• Proto-Oncogene Proteins
• Vascular Cell Adhesion Molecule-1

Topics

• 3T3 Cells
• Animals
• Bone Neoplasms (metabolism, secondary)
• CCN Intercellular Signaling Proteins (metabolism)
• Cell Adhesion
• Cell Line, Tumor
• Cell Movement
• Coculture Techniques
• Culture Media, Conditioned (chemistry)
• Endothelin-1 (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Integrin alpha4beta1 (metabolism)
• Male
• Mice
• Neoplasm Transplantation
• Osteoblasts (cytology, metabolism)
• Osteogenesis
• Prostatic Neoplasms (metabolism)
• Proto-Oncogene Proteins (metabolism)
• RAW 264.7 Cells
• Signal Transduction
• Vascular Cell Adhesion Molecule-1 (metabolism)