骨转移是晚期前列腺癌（PC）常见且无法治愈的后果。播散性肿瘤细胞和转移微环境中的异质骨驻留细胞之间的相互作用启动了这一过程。黑色素瘤分化相关基因 9（mda-9/Syntenin/syndecan 结合蛋白）是在生理和病理条件下在多个器官中表达的促转移基因，包括骨髓源性间充质基质细胞 (BM-MSC)。我们证明肿瘤细胞分泌的 PDGF-AA 通过抑制 MDA-9 依赖性 YAP/MST 信号传导来诱导 BM-MSC 中 CXCL5 的表达。 CXCL5 衍生的肿瘤细胞增殖和免疫抑制是 MDA-9/CXCL5 信号轴的结果，促进 PC 疾病进展。 mda-9 敲除肿瘤细胞表达较少的 PDGF-AA，并且不会发生骨转移。我们的数据记录了 MDA-9/Syntenin 在肿瘤和微环境中调节 PC 骨转移的先前未明确的作用。这项研究为改善与晚期 PC 相关的健康并发症和发病率的转化策略提供了一个框架。

Bone metastasis is a frequent and incurable consequence of advanced prostate cancer (PC). An interplay between disseminated tumor cells and heterogeneous bone resident cells in the metastatic niche initiates this process. Melanoma differentiation associated gene-9 (mda-9/Syntenin/syndecan binding protein) is a prometastatic gene expressed in multiple organs, including bone marrow-derived mesenchymal stromal cells (BM-MSCs), under both physiological and pathological conditions. We demonstrate that PDGF-AA secreted by tumor cells induces CXCL5 expression in BM-MSCs by suppressing MDA-9-dependent YAP/MST signaling. CXCL5-derived tumor cell proliferation and immune suppression are consequences of the MDA-9/CXCL5 signaling axis, promoting PC disease progression. mda-9 knockout tumor cells express less PDGF-AA and do not develop bone metastases. Our data document a previously undefined role of MDA-9/Syntenin in the tumor and microenvironment in regulating PC bone metastasis. This study provides a framework for translational strategies to ameliorate health complications and morbidity associated with advanced PC.