背景：转移性前列腺癌（PCa）预测预后差，存活机会也较低。骨母细胞（OBs）负责骨的合成和矿化，但前列腺腺体中的PCa是否与骨中的OBs合作促进PCa恶性转化仍不清楚。我们旨在阐明初级PCa细胞如何与远端OBs合作并促进导致转移性PCa的恶性循环。 方法：通过Western blot测量N-钙黏蛋白（N-cadherin）、E-钙黏蛋白（E-cadherin）和Twist蛋白表达。通过免疫荧光（IF）检测Twist转位到细胞核中。酶联免疫吸附试验（ELISA）检测人血清样品中的蛋白质水平。通过人细胞因子阵列检测候选蛋白质表达水平。通过原位移植前列腺癌模型和转移性前列腺癌模型分析前列腺肿瘤的生长和转移。免疫组织化学（IHC）染色用于观察ADAM金属蛋白酶结构域9（ADAM9）和WNT1诱导信号通路蛋白1（WISP-1）在组织中的表达。 结果：我们的体内外分析现已发现，表达ADAM9蛋白的初级PCa促使OBs转化为与PCa相关的骨母细胞（PCa-OBs），在骨微环境中诱导WISP-1分泌。骨中WISP-1的上调为前列腺提供了反馈，并通过上皮间质转化（EMT）活性促进了PCa细胞的侵袭性。在患有PCa的患者血清中检测到高水平的WISP-1表达。ADAM9水平在PCa患者的肿瘤组织中被过度表达；ADAM9阻断中断了OB诱导的WISP-1释放，并在原位移植PCa鼠模型中抑制了原发肿瘤的生长和远端转移。 结论：我们的研究表明，ADAM9/WISP-1轴有助于转移性PCa的进展。因此，针对ADAM9/WISP-1轴可能有助于预防PCa细胞的恶性表型。©作者。

Background: Metastatic prostate cancer (PCa) predicts a poor prognosis and lower likelihood of survival. Osteoblasts (OBs) are known to be responsible for the synthesis and mineralization of bone, although it is unclear as to whether PCa in the prostate gland cooperates with OBs in bone to promote PCa malignant transformation. We aimed to elucidate how primary PCa cells cooperate with distal OBs and contribute to the vicious cycle that leads to metastatic PCa. Methods: N-cadherin, E-cadherin, and Twist protein expression were measured by Western blot. Twist translocation into the nucleus was detected by the immunofluorescence (IF) assay. Enzyme-linked immunosorbent assay (ELISA) detected protein levels in human serum samples. Levels of candidate protein expression were examined by the human cytokine array. Prostate tumor growth and metastasis were analyzed by orthotopic and metastatic prostate cancer models, respectively. Immunohistochemistry (IHC) staining was used to observe ADAM metallopeptidase domain 9 (ADAM9) and WNT1 inducible signaling pathway protein 1 (WISP-1) expression in tissue. Results: Our in vitro and in vivo analyses have now discovered that primary PCa expressing ADAM9 protein enables the transformation of OBs into PCa-associated osteoblasts (PCa-OBs), inducing WISP-1 secretion from PCa-OBs in the bone microenvironment. The upregulation of WISP-1 in bone provided feedback to primary PCa and promoted PCa cell aggressiveness via epithelial-mesenchymal transition (EMT) activity. Elevated levels of WISP-1 expression were detected in the serum of patients with PCa. ADAM9 levels were overexpressed in tumor tissue from PCa patients; ADAM9 blockade interrupted OB-induced release of WISP-1 and also suppressed primary tumor growth and distal metastasis in orthotopic PCa mouse models. Conclusion: Our study suggests that the ADAM9/WISP-1 axis assists with metastatic PCa progression. Thus, targeting the ADAM9/WISP-1 axis may help to prevent the malignant phenotypes of PCa cells.© The author(s).