Klymenko Yuliya, Nephew Kenneth P
Cell, Molecular and Cancer Biology Program, Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
Cancers (Basel). 2018 Aug 30;10(9):295. doi: 10.3390/cancers10090295.
Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs through direct cell shedding from the primary tumor into the intra-abdominal cavity that is filled with malignant ascitic effusions. Facilitated by the fluid flow, cells distribute throughout the cavity, broadly seed and invade through peritoneal lining, and resume secondary tumor growth in abdominal and pelvic organs. At all steps of this unique metastatic process, cancer cells exist within a multidimensional tumor microenvironment consisting of intraperitoneally residing cancer-reprogramed fibroblasts, adipose, immune, mesenchymal stem, mesothelial, and vascular cells that exert miscellaneous bioactive molecules into malignant ascites and contribute to EOC progression and metastasis via distinct molecular mechanisms and epigenetic dysregulation. This review outlines basic epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulators, and summarizes current knowledge on reciprocal interactions between each participant of the EOC cellular milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising research directions and potential therapeutic strategies that may encompass epigenetic tailoring as a component of complex EOC treatment are discussed.
上皮性卵巢癌（EOC）的转移扩散主要通过原发性肿瘤的细胞直接脱落进入充满恶性腹水的腹腔来实现。在液流的推动下，细胞在整个腹腔内分布，广泛播种并穿透腹膜内衬侵入，然后在腹部和盆腔器官中重新开始继发性肿瘤生长。在这个独特的转移过程的所有步骤中，癌细胞存在于一个多维肿瘤微环境中，该微环境由腹腔内驻留的癌症重编程成纤维细胞、脂肪细胞、免疫细胞、间充质干细胞、间皮细胞和血管细胞组成，这些细胞将多种生物活性分子释放到恶性腹水中，并通过不同的分子机制和表观遗传失调促进EOC的进展和转移。本综述概述了基本的表观遗传机制，包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA调节因子，并总结了在异常表观遗传串扰的背景下，关于EOC细胞微环境中每个参与者与肿瘤细胞之间相互作用的当前知识。还讨论了可能将表观遗传调整作为复杂EOC治疗组成部分的有前景的研究方向和潜在治疗策略。
