Carcinogenesis Advance Access originally published online on February 6, 2008
Carcinogenesis 2008 29(4):880-886; doi:10.1093/carcin/bgn040
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A protective role of mast cells in intestinal tumorigenesis
Department of Cancer Biology, Vanderbilt University, 771 PRB 23rd and Pierce Avenue Nashville, TN 37232-6840, USA
1 Vanderbilt Microarray Shared Resource, Vanderbilt University, 465 21st Avenue South, MRBIII Room 9274, Nashville, TN 37232, USA
2 Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA
3 Present address: Department of Pediatrics University of Utah, Salt Lake City, UT 84112, USA
* To whom correspondence should be addressed. Tel: 615 322-0375; Fax: 615 936-2911; Email: lynn.matrisian{at}vanderbilt.edu
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.
Abbreviations: mcpt, mast cell protease; Min, multiple intestinal neoplasia; MMC, mucosal mast cell; PCR, polymerase chain reaction
Received November 9, 2007; revised January 8, 2008; accepted January 29, 2008.