A protective role of mast cells in intestinal tumorigenesis

被引:71
作者
Sinnamon, Mark J. [1 ]
Carter, Kathy J. [1 ]
Sims, Lauren P. [2 ]
LaFleur, Bonnie [3 ]
Fingleton, Barbara [1 ]
Matrisian, Lynn M. [1 ]
机构
[1] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Vanderbilt Microarray Shared Resource, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA
关键词
D O I
10.1093/carcin/bgn040
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, AP(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-ki(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.
引用
收藏
页码:880 / 886
页数:7
相关论文
共 55 条
[1]   Human mast cells, bacteria, and intestinal immunity [J].
Bischoff, Stephan C. ;
Kraemer, Sigrid .
IMMUNOLOGICAL REVIEWS, 2007, 217 :329-337
[2]   Transcriptional control of activation-induced cytidine deaminase and error-prone DNA polymerases is functionally mature in the B cells of infants at birth [J].
Bowen, Amber L. ;
Tian, Cuixia ;
LaFleur, Bonnie J. ;
Crowe, James E., Jr. .
HUMAN IMMUNOLOGY, 2006, 67 (1-2) :43-46
[3]  
BRADDING P, 1995, J IMMUNOL, V155, P297
[4]  
CAPRON M, 1978, J IMMUNOL, V121, P2518
[5]   Mast cell tryptases and chymases in inflammation and host defense [J].
Caughey, George H. .
IMMUNOLOGICAL REVIEWS, 2007, 217 :141-154
[6]   At the crossroads of inflammation and cancer [J].
Clevers, H .
CELL, 2004, 118 (06) :671-674
[7]  
Corpet DE, 2003, CANCER EPIDEM BIOMAR, V12, P391
[8]   Murine hypodense eosinophils induce tumour cell apoptosis by a granzyme B-dependent mechanism [J].
Costain, DJ ;
Guha, AK ;
Liwski, RS ;
Lee, TDG .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2001, 50 (06) :293-299
[9]   Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis [J].
Coussens, LM ;
Raymond, WW ;
Bergers, G ;
Laig-Webster, M ;
Behrendtsen, O ;
Werb, Z ;
Caughey, GH ;
Hanahan, D .
GENES & DEVELOPMENT, 1999, 13 (11) :1382-1397
[10]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867