RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma.
RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma.
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DOI：
10.1007/s11605-010-1347-z
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发表时间：
2010-11
影响因子：
3.2
通讯作者：
Allendorf, John D.
中科院分区：
文献类型：
--
作者：
DiNorcia, Joseph;Moroziewicz, Dorota N.;Ippagunta, Nikalesh;Lee, Minna K.;Foster, Mark;Rotterdam, Heidrun Z.;Bao, Fei;Zhou, Yu Shan;Yan, Shi Fang;Emond, Jean;Schmidt, Ann Marie;Allendorf, John D.
关键词：
The receptor for advanced glycation end-products (RAGE) is a cell surface receptor implicated in tumor cell proliferation and migration. We hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor growth in murine models of colorectal carcinoma. Tumorigenesis: Apc1638N/+ mice were crossed with Rage−/− mice in the C57BL/6 background to generate Apc1638N/+/Rage−/− mice. Metastasis: BALB/c mice underwent portal vein injection with CT26 cells (syngeneic) and received daily soluble (s)RAGE or vehicle. Rage−/− mice and Rage+/+ controls underwent portal vein injection with MC38 cells (syngeneic). Rage+/+ mice underwent portal vein injection with MC38 cells after stable transfection with full-length RAGE or mock transfection control. Tumorigenesis: Apc1638N/+/Rage−/− mice had reduced tumor incidence, size, and histopathologic grade. Metastasis: Pharmacological blockade of RAGE with sRAGE or genetic deletion of Rage reduced hepatic tumor incidence, nodules, and burden. Gain of function by transfection with full-length RAGE increased hepatic tumor burden compared to vector control MC38 cells. RAGE signaling plays an important role in tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma. Further work is needed to target the ligand-RAGE axis for possible prophylaxis and treatment of primary and metastatic colorectal carcinoma.
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