Nature：癌细胞转移有逆转的可能性
关于人类乳腺癌细胞的新的研究工作表明，它们与来自骨髓的间充质干细胞（MSCs）进行配合，来推进癌细胞转移。乳腺癌细胞提示MSCs产生一种细胞因子CCL5，它在癌细胞上发生作用，促使它们入侵和转移。重要的是，受到MSC刺激的癌细胞并没有获得一个稳定的转移表现型，相反，它们会在没有背景信号的情况下回到其恶化前状态。这一结果让我们看到一个可能性：癌细胞的转移编程通过以CCL5或其受体为目标在治疗上也许是能够逆转的。
原始出处:
Nature 449, 557-563 (4 October 2007) | doi:10.1038/nature06188; Received 13 April 2007; Accepted 14 August 2007
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
Antoine E. Karnoub1, Ajeeta B. Dash2, Annie P. Vo1, Andrew Sullivan2, Mary W. Brooks1, George W. Bell1, Andrea L. Richardson3, Kornelia Polyak4, Ross Tubo2 & Robert A. Weinberg1
- Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
- Genzyme Corporation, Framingham, Massachusetts 01701, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Correspondence to: Robert A. Weinberg1 Correspondence and requests for materials should be addressed to R.A.W. (Email: weinberg@wi.mit.edu).
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.
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