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Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors

Nature Medicine volume 13, pages 12111218 (2007) | Download Citation

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Abstract

An association between inflammation and cancer has long been recognized, but the cause and effect relationship linking the two remains unclear. Myc is a pleiotropic transcription factor that is overexpressed in many human cancers and instructs many extracellular aspects of the tumor tissue phenotype, including remodeling of tumor stroma and angiogenesis. Here we show in a β-cell tumor model that activation of Myc in vivo triggers rapid recruitment of mast cells to the tumor site—a recruitment that is absolutely required for macroscopic tumor expansion. In addition, treatment of established β-cell tumors with a mast cell inhibitor rapidly triggers hypoxia and cell death of tumor and endothelial cells. Inhibitors of mast cell function may therefore prove therapeutically useful in restraining expansion and survival of pancreatic and other cancers.

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Acknowledgements

We thank P. Besmer (Memorial Sloan-Kettering Institute) for C57BL/6 KitW-sh;KitW-sh mice; F. Rostker, G. Reyes and N. Sheehy (BMS program, UCSF) for technical assistance; K. De Visser, S. Robinson, L. Coussens and D. Hanahan for advice; G. Spinetti for informed comments; and our colleagues for feedback. This work was supported by grants from the National Institutes of Health (NIH) National Cancer Institute (CA098018) and the Juvenile Diabetes Research Foundation (grant 4-2004-372) and by an NIH Fellowship (F32 CA106039) to K.S.

Author information

Author notes

    • Elizabeth R Lawlor

    Present address: Division of Hematology-Oncology, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA.

Affiliations

  1. Cancer Research Institute and Departments of Pathology, Cellular and Molecular Pharmacology, University of California San Francisco, 2340 Sutter Street, San Francisco, California 94143-0875, USA.

    • Laura Soucek
    • , Elizabeth R Lawlor
    • , Ksenya Shchors
    • , Lamorna Brown Swigart
    •  & Gerard I Evan
  2. Department of Medicine, Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, California 94143-0875, USA.

    • Darya Soto

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Corresponding author

Correspondence to Gerard I Evan.

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DOI

https://doi.org/10.1038/nm1649

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