Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
Nat Commun. 2013;4:1795. doi: 10.1038/ncomms2766.
Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.
肿瘤招募间充质干细胞来促进愈合，这诱导它们转化为促进转移的癌相关成纤维细胞。然而，这一过程在分子水平上还了解甚少。在这里，我们表明，CXCL16，一种 CXCR6 的配体，促进间充质干细胞或非常小的胚胎样细胞招募进入前列腺肿瘤。CXCR6 信号刺激间充质干细胞转化为癌相关成纤维细胞，后者分泌基质衍生因子 1，也称为 CXCL12。癌相关成纤维细胞表达的 CXCL12 然后与肿瘤细胞上的 CXCR4 结合，并诱导上皮-间充质转化，最终促进转移到次级肿瘤部位。我们的结果为间充质干细胞招募进入肿瘤以及这一过程如何导致肿瘤转移提供了分子基础。
