RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways
RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways
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DOI：
10.1007/s10350-006-0850-5
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发表时间：
2007-08-01
影响因子：
3.9
通讯作者：
Huang, Emina H.
中科院分区：
文献类型：
--
作者：
Fuentes, Maren K.;Nigavekar, Shraddha S.;Huang, Emina H.
目的：结肠癌是美国第三大最常见的癌症。然而，有关结肠癌发生发展的分子机制尚不完全清楚。本研究旨在探讨晚期糖基化终产物受体和S100P在调节人结肠癌细胞关键特性中的作用。方法：采用Western印迹、逆转录-聚合酶链式反应和定量聚合酶链式反应检测晚期糖基化终产物受体和S100P在结肠癌和配对正常结肠组织中的表达。分析外源S100P对SW480结肠癌细胞株增殖、迁移、丝裂原活化蛋白激酶磷酸化及NFkB活化的影响。结果：虽然晚期糖基化终产物受体在正常和恶性结肠组织中均有表达，但只有正常结肠组织中有S100P的表达。S100P可促进SW480细胞的增殖和迁移。外源S100P可刺激ERK1/2的磷酸化和NFkB的活性。S100P与晚期糖基化终产物受体的相互作用通过免疫共沉淀从SW480细胞中得到证实。晚期糖基化终产物受体的拮抗作用阻断了这种相互作用和S100P对这些细胞的生物学效应。结论：这些数据表明S100P在结肠癌组织中的表达水平高于匹配的正常组织，并且S100P在体外刺激结肠癌细胞的生长、迁移、ERK磷酸化和NFkB激活，提示这种配体/受体对可能是开发新疗法的靶点。
PURPOSE: Colon cancer is the third most prevalent cancer in the United States. However, the molecular mechanisms involved in the development and progression of colon cancer are incompletely understood. This study was initiated to explore the potential role of the receptor for advanced glycation end- products and S100P in modulation of key properties of human colon cancer cells.METHODS: Western blot, reverse transcription- polymerase chain reaction, and quantitative polymerase chain reaction were performed for detection of the receptor for advanced glycation end-products and S100P in colon cancer and matched normal colon. The influence of exogenously added S100P was analyzed on SW480 colon cancer cell line proliferation, migration, phosphorylation of mitogen activated protein kinases, and NFkB activation. To identify the mechanisms involved in these responses, coimmuno-precipitation examining the S100P/ Receptor for advanced glycation end- products interaction and the effects of receptor for advanced glycation end- products inhibition in this interaction were analyzed.RESULTS: Although the receptor for advanced glycation end- products was present in normal and malignant colon specimens, only themalignant specimens expressed S100P. Treatment of SW480 cells with S100P increased proliferation and cell migration. Addition of exogenous S100P stimulated both ERK1/ 2 phosphorylation and NFkB activity. The interaction between S100P and the receptor for advanced glycation end- products was demonstrated by coimmunoprecipitation of these molecules from SW480 cells. Antagonism of the receptor for advanced glycation end- products blocked this interaction and the biologic effects of S100P on these cells.CONCLUSIONS: These data indicate that S100P is expressed at greater levels in colon cancer than matched normal tissue and that S100P stimulates colon cancer cell growth, migration, Erk phosphorylation, and NFkB activation in vitro, suggesting that this ligand/ receptor pair may be targeted for the development of new therapies.