Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells
Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells
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DOI：
10.1038/onc.2010.546
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发表时间：
2011-04-01
期刊：
影响因子：
8
通讯作者：
Miyazono, K.
中科院分区：
文献类型：
--
作者：
Ehata, S.;Johansson, E.;Miyazono, K.
已知正常组织中的干细胞和癌症起始细胞（CIC）富含侧群（SP）细胞。然而，负责调节ABCG 2的表达的因素，参与流出的染料，在SP细胞尚未得到充分的研究。在这里，我们的特点是SP细胞在弥漫型胃癌，并检查了转化生长因子-β（TGF-β）对SP细胞的影响。弥漫型胃癌细胞建立从四个独立的患者普遍含有SP细胞之间的1和4%的总细胞，显示更大的致瘤性比非SP细胞没有。TGF-β通过Smad 2/3与其启动子/增强子的直接结合抑制ABCG 2的转录，并且SP细胞的数量和癌细胞的成瘤能力被TGF-β降低，尽管ABCG 2不直接参与SP细胞的成瘤能力。来自转移部位的癌细胞比亲本癌细胞表达更高水平的ABCG 2，并且包括更大百分比的SP细胞。因此，SP细胞负责弥漫型胃癌的进展，并且TGF-β负性地有助于维持癌内的CIC。Oncogene（2011）30，1693-1705; doi：10.1038/onc.2010.546; 2010年12月6日在线发表
Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-beta (TGF-beta) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-beta repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-beta, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-beta negatively contributes to maintain the CICs within the cancer. Oncogene (2011) 30, 1693-1705; doi:10.1038/onc.2010.546; published online 6 December 2010