Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin α4β1 system
Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin α4β1 system
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DOI：
10.1016/j.canlet.2018.03.050
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Chang, An-Chen;Chen, Po-Chun;Tang, Chih-Hsin
骨转移是前列腺癌（PCa）中常见的现象，与骨折、骨痛和高钙血症等严重并发症相关。转移性癌细胞和骨之间的相互作用对于骨转移的发生和进展至关重要。在我们之前的数据中，我们描述了 Wnt 诱导的分泌蛋白 1/血管细胞粘附分子 1 (WISP-1/VCAM-1) 系统如何参与肿瘤骨相互作用，从而促进人 PCa 细胞运动。在这项研究中，我们发现WISP-1通过诱导成骨细胞中骨形态发生蛋白2（BMP2）、BMP4和骨桥蛋白（OPN）的表达来调节骨矿化。我们还发现 WISP-1 抑制 RANKL 依赖性破骨细胞生成。此外，成骨细胞衍生的WISP-1增强PCa细胞中VCAM-1的表达，随后促进癌细胞与成骨细胞的粘附。此外，PCa细胞中的内皮素-1（ET-1）表达受到成骨细胞来源的WISP-1的调节，WISP-1通过MAPK途径促进成骨细胞中整合素α4β1的表达。用VCAM-1抗体预处理PCa细胞或用整合素α4β1抗体预处理成骨细胞减弱了PCa细胞对成骨细胞的粘附，表明整合素α4β1作为配体捕获粘附于成骨细胞的VCAM-1(+)转移性肿瘤细胞。我们的研究结果表明，成骨细胞来源的 WISP-1 在通过 VCAM-1/整合素 α 4 β 1 系统调节 PCa 细胞与成骨细胞的粘附方面发挥着关键作用。成骨细胞衍生的 WISP-1 是预防和抑制 PCa-骨相互作用的有希望的靶标。 (C) 2018 Elsevier B.V. 保留所有权利。
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 alpha 4 beta 1 expression in osteoblasts via the MAPK pathway. Pretreatment of PCa cells with VCAM-1 antibody or osteoblasts with integrin alpha 4 beta 1 antibody attenuated the adherence of PCa cells to osteoblasts, suggesting that integrin alpha 4 beta 1 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 alpha 4 beta 1 system. Osteoblast-derived WISP-1 is a promising target for the prevention and inhibition of PCa-bone interaction. (C) 2018 Elsevier B.V. All rights reserved.