Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells
Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells
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DOI：
10.1159/000337296
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发表时间：
2012-01-01
期刊：
影响因子：
5
通讯作者：
Yokozaki, Hiroshi
中科院分区：
文献类型：
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作者：
Nishimura, Kanako;Semba, Shuho;Yokozaki, Hiroshi
目的：越来越多的证据表明，癌症相关的成纤维细胞是由骨髓间充质干细胞（BM-MSC）提供的;然而，关于BM-MSC加速癌症侵袭性的机制知之甚少。方法：将胃癌MKN-7细胞与UE 6 E7 T-12骨髓间充质干细胞共培养。通过微阵列分析研究MKN-7细胞中的基因表达谱。两种主要类型的GC（肠型和弥漫型），基因的表达，通过免疫组化检测。结果：UE 6 E7 T-12与MKN-7细胞的直接粘附可诱导MKN-7细胞的增殖和成簇。与UE 6 E7 T-12共培养增加了体外CD 133 + MKN-7细胞的数量，将这些细胞共植入小鼠体内导致皮下肿瘤。发现无翅型MMTV整合位点（WNT）家族成员5A（WNT 5A）和转化生长因子-β（TGF-β）诱导的（TGFBI）基因在直接附着于UE 6 E7 T-12的MKN-7细胞中上调。CD 271 + BM-MSC的募集优先在弥漫型GC的基质中检测到，并且这种类型的GC细胞还显示频繁表达WNT 5A、TGF-β I型受体和CD 133。结论：BM-MSC介导的WNT和TGF-β信号通路的激活被认为通过支持癌症干细胞的重新获得和维持而为癌症进展提供有利的微环境。版权所有（c）2012 S. Karger AG，巴塞尔
Objective: Accumulating evidences suggest that cancer-associated fibroblasts are provided from bone-marrow-derived mesenchymal stem cells (BM-MSCs); however, little is known about the mechanism(s) by which BM-MSCs accelerate cancer aggressiveness. Methods: Gastric carcinoma (GC)-derived MKN-7 cells were cocultured with UE6E7T-12 BM-MSCs. The gene expression profile in MKN-7 cells was investigated by microarray analysis. Between two major types of GCs (intestinal- and diffuse-type), the expression of genes was detected by immunohistochemistry. Results: We found that direct attachment to UE6E7T-12 induced proliferation and cluster formation of MKN-7 cells. Coculture with UE6E7T-12 increased the population of CD133+ MKN-7 cells in vitro and coimplantation of these in mice resulted in subcutaneous tumors in vivo. The wingless-type MMTV integration site (WNT) family member 5A (WNT5A) and transforming growth factor-beta (TGF-beta)-induced (TGFBI) genes were found to be upregulated in MKN-7 cells directly attached to UE6E7T-12. Recruitment of CD271+ BM-MSC was detected preferentially in the stroma of the diffuse-type GC and this type of GC cell also showed frequent expression of WNT5A, TGF-beta type I receptor and CD133. Conclusion: BM-MSC-mediated activations of the WNT and TGF-beta signaling pathways were thought to provide advantageous microenvironments for cancer progression by supporting the reacquisition and maintenance of cancer stem cells. Copyright (c) 2012 S. Karger AG, Basel