Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.
Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.
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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。
DOI：
10.1158/2159-8290.cd-12-0101
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发表时间：
2012-09
期刊：
影响因子：
28.2
通讯作者：
Weinberg RA
中科院分区：
文献类型：
--
作者：
Li HJ;Reinhardt F;Herschman HR;Weinberg RA
肿瘤相关间质的间质细胞是肿瘤细胞行为的关键决定因素。我们主要关注癌细胞与间充质干细胞(MSCs)的相互作用，间充质干细胞被招募到肿瘤基质中，一旦存在，就能够影响癌细胞的表型。我们发现癌细胞来源的白介素1(IL-1)可诱导间充质干细胞分泌前列腺素E2(PGE2)。由此产生的PGE2以自分泌方式工作，与正在进行的旁分泌IL-1信号合作，由MSCs诱导一组细胞因子的表达。然后，前列腺素E_2和细胞因子以旁分泌的方式作用于癌细胞，诱导β-连环蛋白信号的激活和癌症干细胞的形成。这些观察表明，MSCs和衍生细胞类型创造了一个癌症干细胞利基，通过释放PGE2和细胞因子来促进肿瘤的进展。
Mesenchymal cells of the tumor-associated stroma are critical determinants of carcinoma cell behavior. We focus here on interactions of carcinoma cells with mesenchymal stem cells (MSCs), which are recruited to the tumor stroma and, once present, are able to influence the phenotype of the carcinoma cells. We find that carcinoma cell-derived interleukin-1 (IL-1) induces prostaglandin E2 (PGE2) secretion by MSCs. The resulting PGE2 operates in an autocrine manner, cooperating with ongoing paracrine IL-1 signaling, to induce expression of a group of cytokines by the MSCs. The PGE2 and cytokines then proceed to act in a paracrine fashion on the carcinoma cells to induce activation of β-catenin signaling and formation of cancer stem cells. These observations indicate that MSCs and derived cell types create a cancer stem-cell niche to enable tumor progression via release of PGE2 and cytokines.