Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Anticancer Strategies Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Cancer Sci. 2024 May;115(5):1370-1377. doi: 10.1111/cas.16117. Epub 2024 Feb 27.
Cancer stem cells (CSCs) are a long-lived and self-renewing cancer cell population that drives tumor propagation and maintains cancer heterogeneity. They are also implicated in the therapeutic resistance of various types of cancer. Recent studies of CSCs in colorectal cancer (CRC) have uncovered fundamental paradigms that have increased understanding of CSC systems in solid tumors. Colorectal CSCs share multiple biological properties with normal intestinal stem cells (ISCs), including expression of the stem cell marker Lgr5. New evidence suggests that colorectal CSCs manifest substantial heterogeneity, as exemplified by the existence of both actively cycling Lgr5 CSCs as well as quiescent Lgr5 CSCs that are resistant to conventional anticancer therapies. The classical view of a rigid cell hierarchy and irreversible cell differentiation trajectory in normal and neoplastic tissues is now challenged by the finding that differentiated cells have the capacity to revert to stem cells through dynamic physiological reprogramming events. Such plasticity of CSC systems likely underlies both carcinogenesis and therapeutic resistance in CRC. Further characterization of the mechanisms underpinning the heterogeneity and plasticity of CSCs should inform future development of eradicative therapeutic strategies for CRC.
癌症干细胞（CSCs）是一种长寿且自我更新的癌细胞群体，它能够驱动肿瘤的增殖并维持肿瘤的异质性。CSCs 还与多种类型癌症的治疗耐药性有关。最近对结直肠癌（CRC）CSCs 的研究揭示了基本的范例，增加了对实体瘤中 CSC 系统的理解。结直肠 CSCs 与正常肠干细胞（ISCs）具有多种生物学特性，包括干细胞标志物 Lgr5 的表达。新的证据表明，结直肠 CSCs 表现出显著的异质性，例如存在活跃循环的 Lgr5 CSCs 以及对传统抗癌疗法具有抗性的静止 Lgr5 CSCs。在正常和肿瘤组织中，经典的刚性细胞层次结构和不可逆的细胞分化轨迹的观点现在受到挑战，因为发现分化细胞具有通过动态生理重编程事件恢复为干细胞的能力。CSC 系统的这种可塑性可能是 CRC 发生和治疗耐药性的基础。进一步阐明 CSCs 异质性和可塑性的机制，应能为 CRC 的根治性治疗策略的未来发展提供信息。
