Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffre' 5, 90127 Palermo, Italy.
Division of Immunology and Immunogenetics, Department of Biotechnology and Medical and Forensic Biopathological (DIBIMEF), Palermo, Italy.
Mol Aspects Med. 2014 Oct;39:61-81. doi: 10.1016/j.mam.2013.07.001. Epub 2013 Aug 5.
Colorectal tumours are actually considered as aberrant organs, within it is possible to notice a different stage of cell growth and differentiation. Their origin is reported to arise from a subpopulation of tumour cells endowed with, just like the healthy stem cells, self-renewal and aberrant multi-lineage differentiation capacity likely to be called colorectal cancer stem cells (CCSCs). Cancer stem cells (CSCs) fate, since their origin, reflects the influences from their microenvironment (or niche) both in the maintenance of stemness, in promoting their differentiation, and in inducing epithelial-mesenchymal transition, responsible of CSCs dissemination and subsequent formation of metastatic lesions. The tumour cells heterogeneity and their immuno-response resistance nowadays probably responsible of the failure of the conventional therapies, make this research field an open issue. Even more importantly, our increasing understanding of the cellular and molecular mechanisms that regulate CSC quiescence and cell cycle regulation, self-renewal, chemotaxis and resistance to cytotoxic agents, is expected to eventually result in tailor-made therapies with a significant impact on the morbidity and overall survival of colorectal cancer patients.
结直肠肿瘤实际上被认为是异常器官,在其中可以注意到细胞生长和分化的不同阶段。据报道,它们起源于一群具有自我更新和异常多谱系分化能力的肿瘤细胞亚群,这些细胞类似于健康的干细胞,可能被称为结直肠癌症干细胞(CSCs)。癌症干细胞(CSCs)的命运,从它们的起源来看,反映了它们的微环境(或生态位)的影响,在维持干细胞特性、促进其分化以及诱导上皮-间充质转化方面都有影响,后者负责 CSCs 的扩散和随后形成转移病灶。肿瘤细胞的异质性和它们对免疫反应的抵抗性,可能是导致传统疗法失败的原因,这使得该研究领域成为一个悬而未决的问题。更重要的是,我们对调节 CSC 静止和细胞周期调控、自我更新、趋化性以及对细胞毒性药物的抵抗的细胞和分子机制的理解不断加深,有望最终产生针对结直肠癌患者发病率和总体生存率的显著影响的定制疗法。