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Effects of Tumor Microenvironment on Proliferation of Mesenchymal Stem Cells and Its Molecular Mechanism
Qin Xiang, Luo Qing, Zhang Bingyu, Shi Yisong, Yang Li, Song Guanbin*
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering,Chongqing University, Chongqing 400044, China
Abstract: Mesenchymal stem cells (MSCs) have been demonstrated to be a promising targeted antitumor agent. The various tumor-cell-secreted cytokines and chemokines may have a significant impact on MSCs. However，the changes of MSCs cellular characteristics as well as involved molecular mechanism under tumor microenvironment are not fully understood. In this study， we investigated the conditioned medium from hepatocellular carcinoma cells (HCC-CM) on proliferation of rat mesenchymal stem cells (rMSCs) and the possible signal molecules in this procedure. We found that HCC-CM significantly promoted the proliferation and the expression of stromal cell-derived factor-1 (SDF-1) in rMSCs. Western blot showed that ERK1/2 was strongly activated following the stimuli of HCC-CM from 15 min to 2 h. PD98059 significantly inhibited HCC-CM-induced rMSCs ERK1/2 phosphorylation and proliferation. Moreover， AMD3100， the inhibitor of CXCR4， partially disrupted phosphorylation of ERK1/2 as well as HCC-CM-induced proliferation. These results demonstrated that ERK1/2 molecule and SDF-1/ CXCR4 play a significant role in the HCC-CM-induced rMSCs proliferation. This study also provides an insight into the molecular mechanism of MSCs proliferation in response to conditioned medium of tumor cells and lays a foundation for fully understanding the cellular characteristics of MSCs in the remolded tumor microenvironment.
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