Laboratory of Experimental Carcinogenesis (LEC), Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Semin Liver Dis. 2010 Feb;30(1):26-34. doi: 10.1055/s-0030-1247130. Epub 2010 Feb 19.
Increasing evidence suggests that many, perhaps all solid tumors contain a subset of cells that possess functional properties similar to the normal tissue stem cells, including self-renewal, unlimited proliferative capacity, and pluripotency. The hierarchical cancer model that places a cancer stem cell (CSC) population at the apex of tumor formation is based on this notion. The cancer stem cell hypothesis posits that CSCs are responsible not only for tumor initiation, but also generation of metastasis and local recurrence after therapy. Current definitions of the CSC are based only on functional properties regardless of potential cellular origin. Histopathology investigations of chronic liver diseases and experimental studies support the existence of CSCs in liver cancer. In particular, recent advances in microarray technologies utilizing integrative comparative genomic analysis of human hepatocellular carcinoma specimens, cancer cell lines, and transgenic models establish the molecular similarities between CSC and normal tissue stem cells and highlight the importance of CSC for the prognosis of liver cancer patients. The results have also uncovered the key "stemness" and oncogenic pathways frequently disrupted during hepatocarcinogenesis providing the basis for identifying novel therapeutic targets against CSC.
越来越多的证据表明，许多（如果不是全部的话）实体肿瘤中存在一小部分细胞，这些细胞具有类似于正常组织干细胞的功能特性，包括自我更新、无限增殖能力和多能性。基于这一概念，提出了将癌症干细胞（CSC）群体置于肿瘤形成顶端的层次式癌症模型。癌症干细胞假说认为，CSC 不仅负责肿瘤的起始，而且还负责治疗后转移和局部复发的发生。目前对 CSC 的定义仅基于功能特性，而不考虑潜在的细胞起源。慢性肝脏疾病的组织病理学研究和实验研究支持肝癌中存在 CSC。特别是，最近利用人类肝细胞癌标本、癌细胞系和转基因模型的整合比较基因组分析的微阵列技术的进展，确立了 CSC 与正常组织干细胞之间的分子相似性，并强调了 CSC 对肝癌患者预后的重要性。这些结果还揭示了在肝癌发生过程中经常被打乱的关键“干性”和致癌途径，为确定针对 CSC 的新治疗靶点提供了基础。
