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         description: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. New work with human breast cancer cells shows that they cooperate with mesenchymal stem cells (MSCs) derived from the bone marrow to advance metastasis. The breast cancer cells prompt MSCs to produce a cytokine, CCL5, that acts on cancer cells to promote their invasion and metastasis. Significantly, the MSC-stimulated cancer cells do not acquire a stable metastatic phenotype; rather they revert to their pre-malignant state in the absence of contextual signals. This raises the possibility that metastatic programming of cancer cells may be reversed therapeutically by targeting CCL5 or its receptor. Engrafted mesenchymal stem cells (MSCs) promote breast cancer metastasis formation. Breast cancer cells induce MSCs to produce the cytokine CCL5, which then acts on breast tumour cells, enhancing their ability to migrate and extravasate blood vessel at the site of future metastases.
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      headline:Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
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