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RAGE Activation by S100P in Colon Cancer Stimulates Growth, Migration, and Cell Signaling Pathways

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Diseases of the Colon & Rectum

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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 NFκB activation. To identify the mechanisms involved in these responses, coimmunoprecipitation 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 the malignant specimens expressed S100P. Treatment of SW480 cells with S100P increased proliferation and cell migration. Addition of exogenous S100P stimulated both ERK1/2 phosphorylation and NFκB 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 NFκB activation in vitro, suggesting that this ligand/receptor pair may be targeted for the development of new therapies.

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Acknowledgments

The authors thank Takao Hinoi, M.D., Ph.D., Tamara Tucker, B.A. and Mark Hynes B.A. for technical assistance and Diane Simeone, M.D. for critically reading the manuscript.

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Authors and Affiliations

  1. Program in Cellular & Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Maren K. Fuentes M.S.

  2. Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Maren K. Fuentes M.S., Thiruvengadam Arumugam Ph.D. & Craig D. Logsdon Ph.D.

  3. Department of Surgery, TC 2922B, P. O. Box 0331, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan, 48109-0622, USA

    Shraddha S. Nigavekar Ph.D. & Emina H. Huang M.D.

  4. Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Craig D. Logsdon Ph.D.

  5. Department of Surgery, Columbia University, New York, New York, USA

    Ann Marie Schmidt M.D. & Juliet C. Park M.D.

Authors
  1. Maren K. Fuentes M.S.
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  2. Shraddha S. Nigavekar Ph.D.
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  3. Thiruvengadam Arumugam Ph.D.
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  4. Craig D. Logsdon Ph.D.
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  5. Ann Marie Schmidt M.D.
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  6. Juliet C. Park M.D.
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  7. Emina H. Huang M.D.
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Corresponding author

Correspondence to Emina H. Huang M.D..

Additional information

Supported by K0891975 (EHH), Lockton Endowment (CDL), and CA87677 (AMS).

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Fuentes, M.K., Nigavekar, S.S., Arumugam, T. et al. RAGE Activation by S100P in Colon Cancer Stimulates Growth, Migration, and Cell Signaling Pathways. Dis Colon Rectum 50, 1230–1240 (2007). https://doi.org/10.1007/s10350-006-0850-5

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  • DOI: https://doi.org/10.1007/s10350-006-0850-5

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