Microenvironmental regulation of epithelial-mesenchymal transitions in cancer.
Microenvironmental regulation of epithelial-mesenchymal transitions in cancer.
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DOI：
10.1158/0008-5472.can-12-1223
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发表时间：
2012-10-01
期刊：
影响因子：
11.2
通讯作者：
Mittal V
中科院分区：
文献类型：
--
作者：
Gao D;Vahdat LT;Wong S;Chang JC;Mittal V
癌细胞演变成转移性实体是癌症患者死亡的主要原因。上皮细胞向间质细胞转化（EMT）的激活赋予癌细胞侵袭性和转移性，其有利于远端靶器官的成功定殖。在许多癌症中，远端转移与原发性肿瘤的上皮表型相似的观察结果导致了以下推测：募集到靶器官的播散性肿瘤细胞经历了间充质向上皮转化（MET）。然而，MET级联尚未在体内重现，促进MET的细胞和分子调节剂仍然未知。在最近的一份报告中，使用自发性乳腺癌的模型，我们已经表明，骨髓（BM）来源的髓样祖细胞在转移前肺分泌蛋白聚糖多功能蛋白聚糖，诱导转移性肿瘤细胞的MET和加速转移。本文综述了MET研究的最新进展，并概述了微环境和癌细胞之间独特的旁分泌串扰，促进转移器官中的肿瘤生长，并讨论了新的抗转移方法用于癌症治疗的机会。
The evolution of the cancer cell into a metastatic entity is the major cause of death in cancer patients. Activation of epithelial to mesenchymal transition (EMT) endows invasive and metastatic properties upon cancer cells that favor successful colonization of distal target organs. The observation that in many cancers distant metastases resemble the epithelial phenotype of primary tumors has led to speculation that the disseminated tumor cells recruited to the target organs undergo mesenchymal to epithelial transition (MET). However, the MET cascade has not been recapitulated in vivo, and the cellular and molecular regulators that promote MET remain unknown. In a recent report, using a model of spontaneous breast cancer, we have shown that bone marrow (BM)-derived myeloid progenitor cells in the premetastatic lung secrete the proteoglycan versican, which induces MET of metastatic tumor cells and accelerates metastases. This review summarizes recent progress in MET research and outlines a unique paracrine cross talk between the microenvironment and the cancer cells that promotes tumor outgrowth in the metastatic organ and discusses opportunities for novel antimetastatic approaches for cancer therapy.