Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Exp Mol Med. 2020 May;52(5):781-792. doi: 10.1038/s12276-020-0439-4. Epub 2020 May 28.
Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy. Based on the known effects of EndMT on the cardiac toxicity of anticancer therapy and tissue damage of radiation therapy, we propose that EndMT can be targeted as a strategy for overcoming tumor resistance while reducing complications, such as tissue damage. In this review, we discuss EndMT and its roles in damaging cardiac and lung tissues, as well as EndMT-related effects on tumor vasculature and resistance in anticancer therapy. Modulating EndMT in radioresistant tumors and radiation-induced tissue fibrosis can especially increase the efficacy of radiation therapy. In addition, we review the role of hypoxia and reactive oxygen species as the main stimulating factors of tissue damage due to vascular damage and EndMT. We consider drugs that may be clinically useful for regulating EndMT in various diseases. Finally, we argue the importance of EndMT as a therapeutic target in anticancer therapy for reducing tissue damage.
内皮-间质转化（EndMT）涉及内皮细胞向间充质细胞的表型转化，最初是在与胚胎心脏发育相关的研究中发现的。EndMT 可以调节多种过程，如组织纤维化和癌症。最近的研究结果表明，EndMT 与癌症治疗的耐药性有关，如化疗、抗血管生成治疗和放射治疗。基于 EndMT 对癌症治疗的心脏毒性和放射治疗引起的组织损伤的已知影响，我们提出可以将 EndMT 作为一种策略来克服肿瘤耐药性，同时减少并发症，如组织损伤。在这篇综述中，我们讨论了 EndMT 及其在损伤心脏和肺部组织中的作用，以及 EndMT 对肿瘤血管生成和癌症治疗耐药性的影响。在放射性耐药肿瘤和放射诱导的组织纤维化中调节 EndMT 可以特别提高放射治疗的疗效。此外，我们还回顾了缺氧和活性氧作为血管损伤和 EndMT 引起的组织损伤的主要刺激因素的作用。我们考虑了可能在临床上用于调节各种疾病中的 EndMT 的药物。最后，我们认为 EndMT 作为癌症治疗中减少组织损伤的治疗靶点的重要性。
