在癌症中,休眠是指一种临床状态,在这种状态下,微观残留疾病变得不增生,并且在很大程度上对化疗难以治疗。休眠最初是在乳腺癌中描述的,在乳腺癌中,疾病可能几十年都没有被发现,最终导致原始恶性肿瘤的复发和临床表现。一个长的潜伏期可以解释为退出细胞增殖(细胞休眠),或保持低水平残留疾病(肿瘤块休眠)的增殖和细胞死亡之间的平衡。对细胞休眠的研究揭示了定义这种状态的特征。它们包括细胞增殖的停滞,细胞代谢改变,以及独特的细胞依赖性和与微环境的相互作用。这些特征可以由来自不同原发疾病部位的休眠细胞共享。这表明它们之间存在共同的特征。高级别浆液性卵巢癌(HGSOC)通过称为球体的细胞聚集体扩散到整个腹腔。这些生长停滞和治疗抗性细胞是疾病复发的重要因素。在这次审查中,我们讨论了卵巢癌细胞在球体和其他癌症疾病部位的休眠特性之间的异同.这揭示了休眠的元素,如细胞周期控制机制和新陈代谢的变化,在大多数形式的细胞休眠中可能是相似的。然而,球体生物学的HGSOC特定方面,包括细胞外基质组织和微环境,必须是疾病部位特异性的。总的来说,我们对当前文献的批判性回顾强调了HGSOC细胞休眠的地方,这可能为理解癌症细胞休眠的广泛原理提供了更易于处理的实验方法.
In cancer, dormancy refers to a clinical state in which microscopic residual disease becomes non-proliferative and is largely refractory to chemotherapy. Dormancy was first described in breast cancer where disease can remain undetected for decades, ultimately leading to relapse and clinical presentation of the original malignancy. A long latency period can be explained by withdrawal from cell proliferation (cellular dormancy), or a balance between proliferation and cell death that retains low levels of residual disease (tumor mass dormancy). Research into cellular dormancy has revealed features that define this state. They include arrest of cell proliferation, altered cellular metabolism, and unique cell dependencies and interactions with the microenvironment. These characteristics can be shared by dormant cells derived from disparate primary disease sites, suggesting common features exist between them.High-grade serous ovarian cancer (HGSOC) disseminates to locations throughout the abdominal cavity by means of cellular aggregates called spheroids. These growth-arrested and therapy-resistant cells are a strong contributor to disease relapse. In this review, we discuss the similarities and differences between ovarian cancer cells in spheroids and dormant properties reported for other cancer disease sites. This reveals that elements of dormancy, such as cell cycle control mechanisms and changes to metabolism, may be similar across most forms of cellular dormancy. However, HGSOC-specific aspects of spheroid biology, including the extracellular matrix organization and microenvironment, are obligatorily disease site specific. Collectively, our critical review of current literature highlights places where HGSOC cell dormancy may offer a more tractable experimental approach to understand broad principles of cellular dormancy in cancer.