肿瘤干细胞生物学特性及其干性维持机制的研究进展

Advances in the biological characteristics and stem maintenance mechanisms of tumor stem cells

摘要:

肿瘤是威胁人类健康和社会发展最为严重的疾病之一，也是全球第二大常见疾病死因。最新统计数据显示，恶性肿瘤在发达国家已取代心血管疾病成为第一大疾病死因。肿瘤的耐药、转移和复发，仍然是临床治疗中亟需解决的难题。肿瘤干细胞(tumor stem cells, TSCs)是一类具有自我更新、分化潜能、高致瘤性和高耐药性等特征的细胞亚群，能够抵抗放化疗等非特异性治疗手段，在肿瘤发生、转移、耐药和复发中发挥关键作用。肿瘤干细胞标志物、干性维持机制、微环境和代谢重编程等领域已成为了研究热点，最新研究成果为肿瘤干细胞的鉴定和靶向治疗提供了新的靶标和策略。本文对肿瘤干细胞的表面标志物(CD133和CD44等)、自我更新和上皮细胞间充质转化(epithelial mesenchymal transition, EMT)信号通路(Wnt/β-catenin和Hedgehog等)、微环境特征、代谢重编程(糖酵解和氧化磷酸化等)，及其在肿瘤的起始、发展、转移和耐药中的作用进行了综述。

Abstract:

Tumor is one of the most serious diseases that threaten human health and social development, and it is the second most common cause of death worldwide. The latest statistics show that malignant tumors have surpassed cardiovascular disease as the leading cause of death in developed countries. Drug resistance, metastasis, and recurrence of tumors continue to present urgent challenges in clinical treatment. Tumor stem cells (TSCs) are a specific subset of cells that possess high capabilities of self-renewal, differentiation potential, tumorigenicity and drug resistance. They are resistant to non-specific treatment methods such as chemotherapy and radiotherapy, and play a crucial role in tumor initiation, metastasis, drug resistance, and recurrence. The surface markers, stemness maintenance mechanisms, microenvironment, and metabolic reprogramming of TSCs have become areas of intense research focus. The latest research results provide novel targets and strategies for the identification of TSCs and targeted therapy. This paper reviews the surface markers (CD133, CD44, etc.), self-renewal and epithelial mesenchymal transition (EMT) signaling pathways (Wnt/β-catenin, Hedgehog, etc.), microenvironment characteristics, metabolic reprogramming (glycolysis, oxidative phosphorylation, etc.) and their roles in the initiation, development, metastasis and drug resistance of TSCs.