A protective role of mast cells in intestinal tumorigenesis.
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, APC(Min/+)) 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-kit(W-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.
Sinnamon
Mark J
MJ
Department of Cancer Biology, Vanderbilt University, 771 PRB 23rd and Pierce Avenue Nashville, TN 37232-6840, USA.
Carter
Kathy J
KJ
Sims
Lauren P
LP
Lafleur
Bonnie
B
Fingleton
Barbara
B
Matrisian
Lynn M
LM
D000818:Animals; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
D010450:Endopeptidases