Colon Cancer Stem Cells: Promise of Targeted Therapy
Colon Cancer Stem Cells: Promise of Targeted Therapy
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DOI：
10.1053/j.gastro.2009.12.063
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发表时间：
2010-06-01
期刊：
影响因子：
29.4
通讯作者：
Stassi, Giorgio
中科院分区：
文献类型：
--
作者：
Todaro, Matilde;Francipane, Maria Giovanna;Stassi, Giorgio
癌症干细胞（CSCs）的概念最初用于血液系统疾病，后来扩展到实体肿瘤，包括结直肠癌（CRC）。传统的结肠癌发生模型包括癌基因的突变激活和肿瘤抑制基因的失活。肠上皮细胞存在的时间比积累诱导肿瘤的遗传变化所需的时间短，因此研究人员研究了CRC起源于长寿干细胞的概念，而不是来自分化的上皮细胞。结肠CSCs最初是通过CD133糖蛋白的表达来鉴定的，使用一种针对其表位AC133的抗体。目前尚不清楚CD133是否是结肠csc的标记物——其他细胞表面标记物，如上皮特异性抗原、CD44、CD166、Musashi-1、CD29、CD24、富含亮氨酸的含重复g蛋白偶联受体5和醛脱氢酶1，已被提出。除了启动和维持肿瘤生长外，CSCs被认为介导化疗后的癌症复发。我们如何识别和分析结肠CSCs以及设计哪些药物来杀死这种化疗难治性人群？
First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. It is not clear if CD133 is a marker of colon CSCs-other cell surface markers, such as epithelial-specific antigen, CD44, CD166, Musashi-1, CD29, CD24, leucine-rich repeat-containing G-protein-coupled receptor 5, and aldehyde dehydrogenase 1, have been proposed. In addition to initiating and sustaining tumor growth, CSCs are believed to mediate cancer relapse after chemotherapy. How can we identify and analyze colon CSCs and what agents are being designed to kill this chemotherapy-refractory population?