Identification and characterization of tumorigenic liver cancer stem/progenitor cells
Identification and characterization of tumorigenic liver cancer stem/progenitor cells
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DOI：
10.1053/j.gastro.2007.04.025
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发表时间：
2007-06-01
期刊：
影响因子：
29.4
通讯作者：
Guan, Xin-Yuan
中科院分区：
文献类型：
--
作者：
Ma, Stephanie;Chan, Kwok-Wah;Guan, Xin-Yuan
背景和目的：干细胞生物学的最新研究表明，肿瘤是按照异质细胞群的层次结构组织的，并且维持肿瘤形成/生长的能力具体存在于称为癌症干细胞（CSC）的小细胞群中。本研究的目的是识别、分离和表征驱动和维持肝细胞癌 (HCC) 生长和转移的 CSC 群体。方法：使用严重部分肝切除模型鉴定参与肝再生的正常干细胞。根据纯化的 HCC 细胞的致瘤潜力和所表现出的干细胞/祖细胞样特性，对纯化的 HCC 细胞（无论是否表达已识别的正常干细胞表型）进行评估，以确定肝脏 CSC 是否可以或部分通过该表面标记物进行识别。结果：我们报告了从人肝细胞系中鉴定和分离出表达 CD133 表面表型的 CSC 群体。 CD133(+)细胞具有更高的集落形成效率、更高的增殖输出和更强的体内形成肿瘤的能力。这些细胞被赋予与祖细胞相似的特征，包括“干细胞”基因的表达、自我更新的能力以及分化成非肝细胞样谱系的能力。此外，发现 CD133 仅代表人类 HCC 标本中肿瘤细胞群的一小部分。结论：我们报告了 HCC 中以 CD133 表型为特征的 CSC 群体的鉴定。致瘤性肝脏 CSC 的鉴定可以为 HCC 致瘤过程提供新的见解，并可能具有重大的治疗意义。
Background & Aims: Recent efforts in stem cell biology suggest that tumors are organized in a hierarchy of heterogeneous cell populations and that the capability to maintain tumor formation/growth specifically resides in a small population of cells called cancer stem cells (CSCs). The aim of this study is to identify, isolate, and characterize the CSC population that drives and maintains hepatocellular,carcinoma (HCC) growth and metastasis. Methods: Normal stem cells involved in liver regeneration were identified using a severe partial hepatectomy model. Purified HCC cells, with or without expression of the identified normal stem cell phenotype, were evaluated, based on their tumorigenic potential and exhibition of defined stem/progenitor cell-like properties, to determine whether liver CSCs can be or partly be identified by this surface marker. Results: We report the identification and isolation of a population of CSCs expressing a CD133 surface phenotype from human liver cell lines. CD133(+) cells possess a greater colony-forming efficiency, higher proliferative output, and greater ability to form tumor in vivo. These cells are endowed with characteristics similar to those of progenitor cells including the expression of "stemness" genes, the ability to self-renew, and the ability to differentiate into nonhepatocyte-like lineages. Furthermore, CD133 is found to represent only a minority of the tumor cell population in human HCC specimens. Conclusions: We report the identification of a CSC population in HCC characterized by their CD133 phenotype. The identification of tumorigenic liver CSCs could provide new insight into the HCC tumorigenic process and possibly bear great therapeutic implications.