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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells
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Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells

机译：间充质干细胞为癌症干细胞的恢复提供了有利的肿瘤微环境

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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-β (TGF-β)-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-β type I receptor and CD133. Conclusion: BM-MSC-mediated activations of the WNT and TGF-β signaling pathways were thought to provide advantageous microenvironments for cancer progression by supporting the reacquisition and maintenance of cancer stem cells.
机译：目的：越来越多的证据表明，来自骨髓的间充质干细胞（BM-MSC）可提供癌症相关的成纤维细胞。然而，关于BM-MSC加速癌症侵袭性的机制知之甚少。方法：将源自胃癌（GC）的MKN-7细胞与UE6E7T-12 BM-MSC共培养。通过微阵列分析研究了MKN-7细胞中的基因表达谱。在两种主要类型的GC（肠型和弥散型）之间，通过免疫组织化学检测基因的表达。结果：我们发现直接附着到UE6E7T-12可以诱导MKN-7细胞增殖和簇形成。与UE6E7T-12的共培养在体外增加了CD133 + MKN-7细胞的数量，将它们共植入小鼠体内会导致皮下肿瘤。发现无翅型MMTV整合位点（WNT）家庭成员5A（WNT5A）和转化生长因子-β（TGF-β）诱导（TGFBI）基因在直接附着于UE6E7T-12的MKN-7细胞中被上调。在弥漫型GC的基质中优先检测到CD271 + BM-MSC的募集，并且这种类型的GC细胞还显示出WNT5A，TGF-βI型受体和CD133的频繁表达。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获取和维持为癌症的发展提供了有利的微环境。

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