Department of Biochemistry and Molecular Biology, Tulane School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA.
Cancer Metastasis Rev. 2023 Mar;42(1):143-160. doi: 10.1007/s10555-023-10089-z. Epub 2023 Feb 3.
After treatment and surgery, patient tumors can initially respond followed by a rapid relapse, or respond well and seemingly be cured, but then recur years or decades later. The state of surviving cancer cells during the long, undetected period is termed dormancy. By definition, the dormant tumor cells do not proliferate to create a mass that is detectable or symptomatic, but also never die. An intrinsic state and microenvironment that are inhospitable to the tumor would bias toward cell death and complete eradication, while conditions that favor the tumor would enable growth and relapse. In neither case would clinical dormancy be observed. Normal cells and tumor cells can enter a state of cellular senescence after stress such as that caused by cancer therapy. Senescence is characterized by a stable cell cycle arrest mediated by chromatin modifications that cause gene expression changes and a secretory phenotype involving many cytokines and chemokines. Senescent cell phenotypes have been shown to be both tumor promoting and tumor suppressive. The balance of these opposing forces presents an attractive model to explain tumor dormancy: phenotypes of stable arrest and immune suppression could promote survival, while reversible epigenetic programs combined with cytokines and growth factors that promote angiogenesis, survival, and proliferation could initiate the emergence from dormancy. In this review, we examine the phenotypes that have been characterized in different normal and cancer cells made senescent by various stresses and how these might explain the characteristics of tumor dormancy.
经过治疗和手术，患者的肿瘤最初可能会有反应，随后迅速复发，或者反应良好，看似治愈，但几年或几十年后又复发。在长时间未被发现的情况下，存活癌细胞的状态被称为休眠。根据定义，休眠的肿瘤细胞不会增殖形成可检测或有症状的肿块，但也不会死亡。不利于肿瘤的内在状态和微环境会偏向于细胞死亡和完全清除，而有利于肿瘤的条件则会使肿瘤生长和复发。在这两种情况下都不会观察到临床休眠。正常细胞和肿瘤细胞在受到癌症治疗等压力后，可以进入细胞衰老状态。衰老的特征是由染色质修饰介导的稳定细胞周期停滞，导致基因表达变化和涉及许多细胞因子和趋化因子的分泌表型。已经表明衰老细胞表型具有促进肿瘤和抑制肿瘤的双重作用。这些相反力量的平衡提供了一个有吸引力的模型来解释肿瘤休眠：稳定的阻滞和免疫抑制表型可以促进存活，而可逆的表观遗传程序与促进血管生成、存活和增殖的细胞因子和生长因子结合，可以引发休眠的出现。在这篇综述中，我们研究了不同的正常细胞和癌细胞在受到各种压力后表现出的衰老特征，以及这些特征如何解释肿瘤休眠的特征。
