Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle.

Ke Tang, Liang Hu, Jingwei Ma, Huafeng Zhang, Yi Zhang, Yong Li, Ruihua Ma, Shunqun Luo, Dongbo Liu, Guoxian Long, Mei Han, Shunfang Liu, Anping Song, Meizhu Shen, Guoqing Hu, Bo Huang

Index: Stem Cells 33 , 2877-84, (2015)

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Abstract

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.© 2015 AlphaMed Press.