關(guān)于人類乳腺癌細胞的新的研究工作表明,它們與來自骨髓的間充質(zhì)干細胞(MSCs)進行配合,,來推進癌細胞轉(zhuǎn)移,。乳腺癌細胞提示MSCs產(chǎn)生一種細胞因子CCL5,它在癌細胞上發(fā)生作用,,促使它們?nèi)肭趾娃D(zhuǎn)移,。重要的是,受到MSC刺激的癌細胞并沒有獲得一個穩(wěn)定的轉(zhuǎn)移表現(xiàn)型,,相反,,它們會在沒有背景信號的情況下回到其惡化前狀態(tài)。這一結(jié)果讓我們看到一個可能性:癌細胞的轉(zhuǎn)移編程通過以CCL5或其受體為目標(biāo)在治療上也許是能夠逆轉(zhuǎn)的,。
原始出處:
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.