Regulation of CD151 by Hypoxia Controls Cell Adhesion and Metastasis in Colorectal Cancer
Regulation of CD151 by Hypoxia Controls Cell Adhesion and Metastasis in Colorectal Cancer
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DOI：
10.1158/1078-0432.ccr-08-1651
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发表时间：
2008-12-15
影响因子：
11.5
通讯作者：
Tsai, Shaw-Jenq
中科院分区：
文献类型：
--
作者：
Chien, Chun-Wei;Lin, Shih-Chieh;Tsai, Shaw-Jenq
目的：转移的第一步是癌细胞从周围基质和邻近细胞中脱离;然而，癌细胞如何完成这一过程仍不清楚。因此，我们的目的是调查的基本机制，控制早期事件的transmantal.Experimental设计：一百三十七对结直肠癌和正常结肠组织进行了检查，通过免疫组化染色和Western blot的表达CD 151，四跨膜蛋白家族的成员，在细胞粘附和运动中起着重要作用。结果：与正常对照组相比，结肠癌组织中CD 151表达水平明显降低，而与正常对照组相比，结肠癌组织中CD 151表达水平明显降低。CD 151的表达受缺氧诱导因子-1依赖的缺氧应激的负调控。通过缺氧抑制CD 151导致癌细胞从周围基质和邻近细胞脱离，而在再氧合期间恢复CD 151表达促进粘附能力。结论：氧分压对CD 151的调节可能通过调节肿瘤细胞从原发部位脱落并向继发部位归巢而在肿瘤转移中发挥重要作用。
Purpose: The first step of metastasis is the detachment of cancer cells from the surrounding matrix and neighboring cells; however, how cancer cells accomplish this process remains unclear. Thus, we aimed to investigate the underlying mechanism that controls the early event of metastasis.Experimental Design: One hundred and thirty-seven paired colorectal carcinoma and normal colon tissues were examined by immunohistochemical staining and Western blot for the expression of CD151, a member of the tetraspanin family that plays important roles in cell adhesion and motility. The effect of CD151 on cancer cell adhesion was investigated under normoxia and hypoxia conditions.Results: The level of CD151 was down-regulated in colon cancer compared with the paired normal counterparts. Expression of CD151 was negatively regulated by hypoxia inducible factor-1-dependent hypoxic stress. Suppression of CD151 by hypoxia caused the detachment of cancer cells from the surrounding matrix and neighboring cells whereas restoration of CD151 expression during reoxygenation facilitated the adhesion capacity. Clinical examination further showed that metastasized cancer cells expressed a greater level of CD151 compared with that of primary tumor.Conclusion: Regulation of CD151 by oxygen tension may play an important role in cancer metastasis by regulating the detachment from the primary site and homing in the secondary site.