RAGE Signaling Significantly Impacts Tumorigenesis and Hepatic Tumor Growth in Murine Models of Colorectal Carcinoma

Joseph DiNorcia, Dorota N. Moroziewicz, Nikalesh Ippagunta, Minna K. Lee, Mark Foster, Heidrun Z. Rotterdam, Fei Bao, Yu Shan Zhou, Shi Fang Yan, Jean Emond, Ann Marie Schmidt, John D. Allendorf

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1680-1690
Number of pages11
JournalJournal of Gastrointestinal Surgery
Volume14
Issue number11
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Colon cancer
  • Colorectal carcinoma
  • RAGE
  • Rage knockout mice
  • Receptor for advanced glycation end-products
  • sRAGE

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