Klymenko Yuliya, Kim Oleg, Stack M Sharon
Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA.
Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Cancers (Basel). 2017 Aug 9;9(8):104. doi: 10.3390/cancers9080104.
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC.
与大多数通过血行转移的上皮性恶性肿瘤不同，上皮性卵巢癌（EOC）的转移主要通过体腔播散发生，其特征为肿瘤细胞从原发肿瘤脱落，避免因脱离而诱导的细胞死亡（失巢凋亡），以单个细胞和多细胞聚集体（MCAs）的形式在整个腹腔内移动，黏附并破坏腹膜间皮衬里，以及在间皮下基质中锚定和增殖以形成广泛播散的转移灶。这种特殊的微环境高度允许表型可塑性，使间质向上皮（MET）和上皮向间质（EMT）转变。在本综述中，我们总结了在EMT背景下关于EOC异质性的当前知识，概述了卵巢癌中EMT的主要调节因子，探讨了EMT与EOC化疗耐药性方面的争议，并强调了用于理解EOC中EMT/MET的计算建模方法。
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