摘要
间充质干细胞(mesenchymal stem cells,MSCs)是一类具有靶向迁移特性的潜在抗瘤细胞。肿瘤微环境中的生长因子和趋化因子可能对MSCs的生物学行为产生显著影响,但MSCs在肿瘤微环境中的生物学行为变化规律及其机理还并不清楚。该文探究了大鼠肝癌细胞条件培养基(conditioned medium from hepatocellular carcinoma cells,HCC-CM)对大鼠间充质干细胞(rat mesen-chymal stem cells,rMSCs)增殖的影响及其机理。研究发现,HCC-CM能显著促进rMSCs的增殖和基质衍生因子-1(stromal derived factor-1,SDF-1)的表达。Western blot检测发现,HCC-CM在15 min至2 h均显著上调rMSCs ERK1/2磷酸化,PD98059可完全消除HCC-CM诱导的ERK1/2磷酸化并同时阻断HCC-CM诱导的rMSCs增殖。趋化因子C-X-C受体4(Chemokine C-X-C motif 4,CXCR4)抑制剂AMD3100部分抑制ERK1/2磷酸化,同时也部分抑制了HCC-CM促rMSCs增殖。结果揭示了HCC-CM对rMSCs增殖的影响以及ERK1/2信号分子和SDF-1/CXCR4在HCC-CM促rMSCs增殖过程中的作用,为全面了解MSCs在重塑的肿瘤微环境中生物学行为的变化规律奠定了基础。
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. How- ever, the changes of MSCs cellular characteristics as well as involved molecular mechanism under tumor microen- vironment are not fully understood. In this study, we investigated the conditioned medium from hepatocellular car- cinoma 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 rain to 2 h. PD98059 significantly inhibited HCC-CM-induced rMSCs ERK1/2 phos- phorylation 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.
出处
《中国细胞生物学学报》
CAS
CSCD
北大核心
2013年第8期1094-1102,共9页
Chinese Journal of Cell Biology
基金
中央高校基本科研业务费项目(批准号:CDJZR11230011)
第三批重庆市高等学校优秀人才支持计划项目(批准号:2011-32)资助的课题~~
关键词
肝癌细胞
条件培养基
间充质干细胞
增殖
分子机理
hepatoma cells
conditioned medium
mesenchymal stem cells （MSCs）
proliferation
molecu-lar mechanism
作者简介
通讯作者。Tel：023—65102507，E—mail：song9973@126．com
