Enhanced Cell Migration and Invasion of CD133+ Pancreatic Cancer Cells Cocultured With Pancreatic Stromal Cells
Enhanced Cell Migration and Invasion of CD133+ Pancreatic Cancer Cells Cocultured With Pancreatic Stromal Cells
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DOI：
10.1002/cncr.25121
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发表时间：
2010-07-15
期刊：
影响因子：
6.2
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Moriyama, Taiki;Ohuchida, Kenoki;Tanaka, Masao
背景技术背景：近年来，肿瘤干细胞已被报道为胰腺癌以及其他癌症的新的治疗靶点，但这些细胞的具体作用尚不清楚。方法：作者研究了CD 133（+）细胞在胰腺癌中的功能作用，CD 133（+）细胞是公认的肿瘤干细胞候选者之一。通过定量实时逆转录聚合酶链反应和流式细胞术评估人胰腺癌和癌细胞系中的CD 133表达。接下来，他们使用2种胰腺癌细胞系比较了CD 133（+）和CD 133（-）细胞增殖、迁移和侵袭的能力。特别是，他们评估了CD 133（+）细胞和原代胰腺基质细胞之间的关系。研究结果：CD 133在人胰腺癌组织和部分癌细胞系中表达，而在正常胰腺上皮细胞和胰腺间质细胞中几乎不表达。通过流式细胞术分离的CD 133（+）细胞显示在非贴壁条件下细胞增殖增加（P <0.01），并且增强迁移和侵袭，特别是当与原代胰腺基质细胞共培养时（P <0.001）。趋化因子相关受体4（CXCR 4）在CD 133（+）细胞中显著过表达，可能是与胰腺基质细胞共培养的细胞侵袭能力增加的原因，胰腺基质细胞表达CXCR 4的配体基质衍生因子1。结论：这些数据表明，CD 133（+）细胞表现出更积极的行为，如增加细胞增殖，迁移和侵袭，特别是在胰腺基质细胞的存在。针对CD 133（+）癌细胞与间质细胞相互作用的靶向治疗有望成为胰腺癌治疗的新途径。Cancer 2010;116：3357-68. (C)2010美国癌症协会
BACKGROUND: Recently, cancer stem cells have been reported as a new therapeutic target in pancreatic cancer as well as other cancers, but the specific role of these cells is unknown. METHODS: The authors investigated the functional roles of CD133(+) cells, 1 of the putative cancer stem cell candidates in pancreatic cancer. CD133 expression was assessed in human pancreatic cancer and cancer cell lines by quantitative real-time reverse transcriptase polymerase chain reaction and flow cytometry. Next, they compared the ability of CD133(+) and CD133(-) cells to proliferate, migrate, and invade using 2 pancreatic cancer cell lines. In particular, they evaluated the relationship between CD133(+) cells and primary pancreatic stromal cells. RESULTS: CD133 was expressed in primary human pancreatic cancer tissues and some cancer cell lines, whereas there was little expression in primary normal pancreatic epithelial cells and primary pancreatic stromal cells. CD133(+) cells, isolated by flow cytometry, showed increased cell proliferation under anchorage-independent conditions (P < .01), and enhanced migration and invasion, particularly when cocultured with primary pancreatic stromal cells (P < .001). Chemokine-related receptor-4 (CXCR4), markedly overexpressed in CD133(+) cells, may be responsible for the increased invasive ability of the cells cocultured with pancreatic stromal cells, which express stromal derived factor-1, the ligand to CXCR4. CONCLUSIONS: These data suggest that CD133(+) cells exhibit more aggressive behavior, such as increased cell proliferation, migration, and invasion, especially in the presence of pancreatic stromal cells. The targeting therapy for the interaction between CD133(+) cancer cells and stromal cells may be a new approach for the treatment of pancreatic cancer. Cancer 2010;116:3357-68. (C) 2010 American Cancer Society.