title: RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma.
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.
  
  
  METHODS
  Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the C57BL/6 background to generate Apc (1638N/+)/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: Apc (1638N/+)/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: DiNorcia
authors.forename: Dorota N
authors.initials: DN
authors.lastname: Moroziewicz
authors.forename: Nikalesh
authors.initials: N
authors.lastname: Ippagunta
authors.forename: Minna K
authors.initials: MK
authors.lastname: Lee
authors.forename: Mark
authors.initials: M
authors.lastname: Foster
authors.forename: Heidrun Z
authors.initials: HZ
authors.lastname: Rotterdam
authors.forename: Fei
authors.initials: F
authors.lastname: Bao
authors.forename: Yu Shan
authors.initials: YS
authors.lastname: Zhou
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Jean
authors.initials: J
authors.lastname: Emond
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: John D
authors.initials: JD
authors.lastname: Allendorf
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000503:physiopathology; D017127:Glycation End Products, Advanced; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
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