Ahmed Nuzhat, Stenvers Kaye L
Women's Cancer Research Centre, Royal Women's Hospital , Parkville, VIC , Australia ; Department of Obstetrics and Gynaecology, University of Melbourne , Parkville, VIC , Australia ; Reproductive Development and Cancer Laboratory, Prince Henry's Institute for Medical Research , Melbourne, VIC , Australia.
Front Oncol. 2013 Sep 25;3:256. doi: 10.3389/fonc.2013.00256.
More than one third of ovarian cancer patients present with ascites at diagnosis, and almost all have ascites at recurrence. The presence of ascites correlates with the peritoneal spread of ovarian cancer and is associated with poor disease prognosis. Malignant ascites acts as a reservoir of a complex mixture of soluble factors and cellular components which provide a pro-inflammatory and tumor-promoting microenvironment for the tumor cells. Subpopulations of these tumor cells exhibit cancer stem-like phenotypes, possess enhanced resistance to therapies and the capacity for distal metastatic spread and recurrent disease. Thus, ascites-derived malignant cells and the ascites microenvironment represent a major source of morbidity and mortality for ovarian cancer patients. This review focuses on recent advances in our understanding of the molecular, cellular, and functional characteristics of the cellular populations within ascites and discusses their contributions to ovarian cancer metastasis, chemoresistance, and recurrence. We highlight in particular recent translational findings which have used primary ascites-derived tumor cells as a tool to understand the pathogenesis of the disease, yielding new insights and targets for therapeutic manipulation.
超过三分之一的卵巢癌患者在诊断时出现腹水,几乎所有患者在复发时都有腹水。腹水的存在与卵巢癌的腹膜扩散相关,并与疾病预后不良有关。恶性腹水是可溶性因子和细胞成分的复杂混合物的储存库,为肿瘤细胞提供了促炎和促肿瘤的微环境。这些肿瘤细胞亚群表现出癌症干细胞样表型,对治疗具有增强的抗性以及远端转移扩散和复发性疾病的能力。因此,腹水来源的恶性细胞和腹水微环境是卵巢癌患者发病和死亡的主要来源。本综述重点关注我们对腹水中细胞群体的分子、细胞和功能特征的最新认识进展,并讨论它们对卵巢癌转移、化疗耐药性和复发的影响。我们特别强调最近的转化研究结果,这些研究使用原发性腹水来源的肿瘤细胞作为了解疾病发病机制的工具,为治疗干预带来了新的见解和靶点。