肝细胞癌中的四种癌症干细胞生态位
A quartet of cancer stem cell niches in hepatocellular carcinoma
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影响因子:11.8
分区:医学2区 / 生化与分子生物学2区 细胞生物学2区
发表日期:2024 Oct
作者:
Neha Balaji, Samiksha Kukal, Anjali Bhat, Nikita Pradhan, Shilpi Minocha, Saran Kumar
DOI:
10.1016/j.cytogfr.2024.08.007
摘要
肝细胞癌（HCC）是最常见的原发性肝癌类型，以其侵袭性行为和预后不良而闻名。癌症干细胞理论假设存在一小群具有自我更新能力的细胞，称为癌症干细胞（CSCs），该理论为理解HCC的多种临床和分子特征提供了见解，如肿瘤异质性、代谢适应性、治疗抗性和复发。这些CSCs在肿瘤微环境（TME）中得到培养，在这里，内在和外在因素的混合创造出支持肿瘤生长的生态位，该生态位在空间和时间上不断演变，从而增强肿瘤的复杂性。本文详细介绍了肝CSC（HCSCs）的起源及影响其干细胞样特性的因素。重点讨论了HCSCs与TME（缺氧、血管、侵袭和免疫生态位）之间的相互交流，探索了相关信号通路以及这些相互作用如何调控CSC的恶性特性。此外，还讨论了靶向HCSC生态位的潜在治疗策略及其在临床实践中的潜在应用。
Abstract
Hepatocellular Carcinoma (HCC), the most prevalent type of primary liver cancer, is known for its aggressive behavior and poor prognosis. The Cancer Stem Cell theory, which postulates the presence of a small population of self-renewing cells called Cancer Stem Cells (CSCs), provides insights into various clinical and molecular features of HCC such as tumor heterogeneity, metabolic adaptability, therapy resistance, and recurrence. These CSCs are nurtured in the tumor microenvironment (TME), where a mix of internal and external factors creates a tumor-supportive niche that is continuously evolving both spatially and temporally, thus enhancing the tumor's complexity. This review details the origins of hepatic CSCs (HCSCs) and the factors influencing their stem-like qualities. It highlights the reciprocal crosstalk between HCSCs and the TME (hypoxic, vascular, invasive, and immune niches), exploring the signaling pathways involved and how these interactions control the malignant traits of CSCs. Additionally, it discusses potential therapeutic approaches targeting the HCSC niche and their possible uses in clinical practice.