Journal of Gastrointestinal Surgery

, Volume 14, Issue 11, pp 1680–1690 | Cite as

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
2010 SSAT Plenary Presentation
First Online:
Received:
Accepted:

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.

Keywords

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

Acknowledgments

This work was generously supported by the I.W. Foundation and an institutional Ruth L. Kirschstein National Research Service Award (T32 HL 007854-14).

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Copyright information

© The Society for Surgery of the Alimentary Tract 2010

Authors and Affiliations

  • Joseph DiNorcia
    • 1
  • Dorota N. Moroziewicz
    • 1
  • Nikalesh Ippagunta
    • 1
  • Minna K. Lee
    • 1
  • Mark Foster
    • 1
  • Heidrun Z. Rotterdam
    • 2
  • Fei Bao
    • 2
  • Yu Shan Zhou
    • 1
  • Shi Fang Yan
    • 1
  • Jean Emond
    • 1
  • Ann Marie Schmidt
    • 1
    • 3
  • John D. Allendorf
    • 1
    • 4
  1. 1.Department of Surgery, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Department of Pathology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  3. 3.Department of Medicine, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  4. 4.New YorkUSA

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