Journal Article

A protective role of mast cells in intestinal tumorigenesis

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

in Carcinogenesis

Volume 29, issue 4, pages 880-886
Published in print April 2008 | ISSN: 0143-3334
Published online February 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn040
A protective role of mast cells in intestinal tumorigenesis

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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.

Journal Article.  4822 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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