A protective role of mast cells in intestinal tumorigenesis

Mark J. Sinnamon, Kathy J. Carter, Lauren P. Sims, Bonnie Lafleur, Barbara Fingleton, Lynn M. Matrisian

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Mast cells have been observed in numerous types of tumors; however, their role in carcinogenesis remains poorly understood. The majority of epidemiological evidence suggests a negative association between the presence of mast cells and tumor progression in breast, lung and colonic neoplasms. Intestinal adenomas in the multiple intestinal neoplasia (Min, APCMin/+) mouse displayed increased numbers of mast cells and increased abundance of mast cell-associated proteinases as determined by transcriptional profiling with the Hu/Mu ProtIn microarray. To examine the role of mast cells in intestinal tumorigenesis, a mutant mouse line deficient in mast cells, Sash mice (c-kitW-sh/W-sh), was crossed with the Min mouse, a genetic model of intestinal neoplasia. The resulting mast cell-deficient Min-Sash mice developed 50% more adenomas than littermate controls and the tumors were 33% larger in Min-Sash mice. Mast cell deficiency did not affect tumor cell proliferation; however, apoptosis was significantly inhibited in mast cell-deficient mice. Mast cells have been shown to act as critical upstream regulators of numerous inflammatory cells. Neutrophil, macrophage and T cell populations were similar between Min and Min-Sash mice; however, eosinophils were significantly less abundant in tumors obtained from Min-Sash animals. These results indicate a protective, antitumor role of mast cells in a genetic model of early-stage intestinal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)880-886
Number of pages7
JournalCarcinogenesis
Volume29
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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