Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β.
Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β.
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DOI：
10.1002/ijc.28598
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发表时间：
2014-06-01
影响因子：
6.4
通讯作者：
Iezzi, Giandomenica
中科院分区：
文献类型：
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作者：
Mele, Valentina;Muraro, Manuele G.;Calabrese, Diego;Pfaff, Dennis;Amatruda, Nunzia;Amicarella, Francesca;Kvinlaug, Brynn;Bocelli-Tyndall, Chiara;Martin, Ivan;Resink, Therese J.;Heberer, Michael;Oertli, Daniel;Terracciano, Luigi;Spagnoli, Giulio C.;Iezzi, Giandomenica
间充质干/基质细胞（MSC）是多能前体细胞，具有归巢至原发性和转移性肿瘤部位的能力，在那里它们可以整合到肿瘤相关基质中。然而，它们与癌细胞相互作用的分子机制和结果尚未完全阐明。在这项研究中，我们研究了骨髓来源的MSC对人结直肠癌（CRC）细胞在体外和体内介导的作用。我们发现，MSC触发上皮间充质转化（EMT）在体外肿瘤细胞，如所示的EMT相关基因的上调，下调E-钙粘蛋白和收购间充质形态。这些作用需要细胞与细胞的接触，并通过与肿瘤细胞共培养后在MSC上新表达的表面结合的TGF-β介导。在体内由MSC条件CRC细胞形成的肿瘤块较大，其特征在于较高的血管密度，降低E-钙粘蛋白表达和间充质标志物的表达增加。此外，MSC条件的肿瘤细胞显示出体外侵袭性增加和体内侵袭外周组织的能力增强。因此，通过促进EMT相关现象，MSC似乎有利于CRC细胞获得侵袭性表型。
Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor sites, where they can integrate into the tumor-associated stroma. However, molecular mechanisms and outcome of their interaction with cancer cells have not been fully clarified. In this study, we investigated the effects mediated by bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC triggered epithelial-to-mesenchymal transition (EMT) in tumor cells in vitro, as indicated by upregulation of EMT-related genes, downregulation of E-cadherin and acquisition of mesenchymal morphology. These effects required cell-to-cell contact and were mediated by surface-bound TGF-β newly expressed on MSC upon coculture with tumor cells. In vivo tumor masses formed by MSC-conditioned CRC cells were larger and characterized by higher vessel density, decreased E-cadherin expression and increased expression of mesenchymal markers. Furthermore, MSC-conditioned tumor cells displayed increased invasiveness in vitro and enhanced capacity to invade peripheral tissues in vivo. Thus, by promoting EMT-related phenomena, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells.
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影响因子：
8.8
作者：
通讯作者：
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癌症刺激的间充质干细胞通过前列腺素 E2 信号传导创建癌干细胞生态位。
影响因子：
28.2
作者：
Li HJ;Reinhardt F;Herschman HR;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
4.5
作者：
Karamitopoulou, E.;Zlobec, I.;Lugli, A.
通讯作者：
Lugli, A.
影响因子：
5.2
作者：
Lazennec, Gwendal;Jorgensen, Christian
通讯作者：
Jorgensen, Christian
脂肪组织干细胞移植对前列腺肿瘤的影响。
影响因子：
2.8
作者：
Lin, Guiting;Yang, Rong;Banie, Lia;Wang, Guifang;Ning, Hongxiu;Li, Long-Cheng;Lue, Tom F.;Lin, Ching-Shwun
通讯作者：
Lin, Ching-Shwun