Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
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DOI：
10.1038/nature06188
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发表时间：
2007-10-04
期刊：
影响因子：
64.8
通讯作者：
Weinberg, Robert A.
中科院分区：
文献类型：
--
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
间充质干细胞近期被发现定位于乳腺癌，它们融入肿瘤相关的间质中。然而，间充质干细胞（或其衍生物）在肿瘤病理生理学中的作用尚未被阐明。在此，我们证明当骨髓来源的人类间充质干细胞与原本弱转移性的人类乳腺癌细胞混合，并且将这种细胞混合物引入皮下部位并使其形成肿瘤异种移植物时，会导致癌细胞的转移能力大幅增强。乳腺癌细胞刺激间充质干细胞从头分泌趋化因子CCL5（也称为RANTES），然后它以旁分泌的方式作用于癌细胞，增强其运动性、侵袭性和转移能力。这种增强的转移能力是可逆的，并且依赖于通过趋化因子受体CCR5的CCL5信号传导。总之，这些数据表明肿瘤微环境通过引发癌细胞表型的可逆变化促进转移扩散。
Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.