Journal
STEM CELLS
Volume 33, Issue 9, Pages 2877-2884Publisher
WILEY
DOI: 10.1002/stem.2076
Keywords
Malignant fluids; Mesenchymal stem cells; Floating tumorigenic cells; Glutamine/ammonium cycle
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Funding
- National Basic Research Program of China [2014CB542100]
- National Science Fund for Distinguished Young Scholars of China [81225021]
- National Natural Science Foundation of China [81472653]
- Special Fund of Health Public Welfare Profession of China [201302018]
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How mesenchymal stem cells (MSCs) promote tumor growth remains incompletely understood. Here, we show that mesenchymal stem-like cells (MSLCs) are commonly present in malignant pleural effusion or ascites of cancer patients, where they directly interact with tumor cells. Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. As a result, MSLCs exert tumor-promoting effects by enhancing the proliferation and colony formation of tumor-repopulating cells. The underlying molecular basis involves MSLC release of glutamine to tumorigenic cells. Inhibition of glutamine uptake impedes MSC-mediated tumor-promoting effects. More intriguingly, MSLCs take up tumor cell-released ammonium that, in turn, favors MSLC growth. Thus, glutamine and ammonium form a vicious cycle between MSLCs and tumorigenic cells. These findings suggest a potential clinical application by targeting MSLCs in patients with malignant pleural effusions or ascites.
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