Department of Pharmacology & Chemical Biology and UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Am J Physiol Cell Physiol. 2022 Jul 1;323(1):C125-C132. doi: 10.1152/ajpcell.00049.2022. Epub 2022 May 18.
Ovarian cancer is a highly aggressive disease with poor survival rates in part due to diagnosis after dissemination throughout the peritoneal cavity. It is well-known that inflammatory signals affect ovarian cancer dissemination. Inflammation is a hallmark of cellular senescence, a stable cell cycle arrest induced by a variety of stimuli including many of the therapies used to treat patients with ovarian cancer. Indeed, recent work has illustrated that ovarian cancer cells in vitro, mouse models, and patient tumors undergo senescence in response to platinum-based or poly(ADP-ribose) polymerase (PARP) inhibitor therapies, standard-of-care therapies for ovarian cancer. This inflammatory response, termed the senescence-associated secretory phenotype (SASP), is highly dynamic and has pleiotropic roles that can be both beneficial and detrimental in cell-intrinsic and cell-extrinsic ways. Recent data on other cancer types suggest that the SASP promotes metastasis. Here, we outline what is known about the SASP in ovarian cancer and discuss both how the SASP may promote ovarian cancer dissemination and strategies to mitigate the effects of the SASP.
卵巢癌是一种侵袭性很强的疾病，存活率很低，部分原因是在腹腔扩散后才被诊断出来。众所周知，炎症信号会影响卵巢癌的扩散。炎症是细胞衰老的一个标志，细胞衰老是一种由多种刺激诱导的稳定的细胞周期停滞，这些刺激包括许多用于治疗卵巢癌患者的疗法。事实上，最近的研究表明，体外培养的卵巢癌细胞、小鼠模型和患者肿瘤在铂类或聚（ADP-核糖）聚合酶（PARP）抑制剂治疗、卵巢癌的标准治疗下会发生衰老。这种炎症反应被称为衰老相关分泌表型（SASP），它具有高度动态性和多效性，可以通过内在和外在的方式对细胞产生有益和有害的影响。最近关于其他癌症类型的研究表明，SASP 促进了转移。在这里，我们概述了卵巢癌中 SASP 的已知情况，并讨论了 SASP 如何促进卵巢癌的扩散以及减轻 SASP 影响的策略。
