Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice
Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice
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DOI：
10.1038/sj.onc.1210920
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发表时间：
2008-04-01
期刊：
影响因子：
8
通讯作者：
Amici, A.
中科院分区：
文献类型：
--
作者：
Galie, M.;Konstantinidou, G.;Amici, A.
肿瘤微环境招募具有异常促血管生成和侵袭表型的间充质细胞。目前尚不清楚间充质肿瘤细胞（MTCs）是否来源于成熟成纤维细胞的激活或其干细胞前体。然而，肿瘤中的基质细胞活化在几个方面类似于通常在修复过程如伤口愈合期间发生的间充质重排。间充质干细胞（Mesenchymal stem cells，MSCs）在发育和修复过程中起着至关重要的作用，并具有非凡的促血管生成潜力，在此基础上，它们被认为在治疗缺血性疾病方面显示出巨大的前景。在这里，我们表明，MTCs具有促血管生成的潜力，他们分享最知名的促血管生成因子与骨髓间充质干细胞的转录表达。我们还发现，MTCs和MSC具有相同的干细胞相关基因的分子特征，并且当与同基因动物中的癌细胞共植入时，MSC可能通过支持血管生成开关来确定早期肿瘤的外观。我们的数据（1）揭示了MTC的促血管生成表型的关键方面，（2）强烈表明它们的干细胞来源和（3）信号MSC在肿瘤促进条件下的治疗用途的风险。
Tumor microenvironment in carcinomas recruits mesenchymal cells with an abnormal proangiogenic and invasive phenotype. It is not clear whether mesenchymal tumor cells (MTCs) derive from the activation of mature fibroblasts or from their stem cell precursors. However, stromal cell activation in tumors resembles in several aspects the mesenchymal rearrangement which normally occurs during reparative processes such as wound healing. Mesenchymal stem cells (MSCs) play a crucial role in developmental and reparative processes and have extraordinary proangiogenic potential, on the basis of which they are thought to show great promise for the treatment of ischemic disorders. Here, we show that MTCs have proangiogenic potential and that they share the transcriptional expression of the best-known proangiogenic factors with MSCs. We also found that MTCs and MSCs have the same molecular signature for stemness-related genes, and that when co-implanted with cancer cells in syngeneic animals MSCs determine early tumor appearance, probably by favoring the angiogenic switch. Our data (1) reveal crucial aspects of the proangiogenic phenotype of MTCs, (2) strongly suggest their stem origin and (3) signal the risk of therapeutic use of MSCs in tumor-promoting conditions.