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

Nat Med. 2007 Oct;13(10):1211-8. doi: 10.1038/nm1649. Epub 2007 Sep 30.

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 beta-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 beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / metabolism
  • Femur / cytology
  • Gene Expression Regulation, Neoplastic
  • Immunohistochemistry
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neovascularization, Pathologic / etiology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / etiology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / physiology*

Substances

  • Ccl2 protein, mouse
  • Ccl5 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL5
  • Proto-Oncogene Proteins c-myc