Open AccessBrief Report: Human Mesenchymal Stem‐Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine‐Ammonium Cycle
Author(s) -
Tang Ke,
Hu Liang,
Ma Jingwei,
Zhang Huafeng,
Zhang Yi,
Li Yong,
Ma Ruihua,
Luo Shunqun,
Liu Dongbo,
Long Guoxian,
Han Mei,
Liu Shunfang,
Song Anping,
Shen Meizhu,
Hu Guoqing,
Huang Bo
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2076
Subject(s) - biology , mesenchymal stem cell , glutamine , stem cell , microbiology and biotechnology , ammonium , cell growth , cell cycle , cell , biochemistry , amino acid , chemistry , organic chemistry
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. S tem C ells 2015;33:2877—2884