Abstract:
:Mast cells constitutively express ß-catenin and expand in solid tumors such as colon and skin cancer. However, the role of ß-catenin signaling in mast cells and the cause or effect of mast cell expansion and tumor growth has yet to be established. In earlier studies we used mast cell depletion and protease staining approaches, to provide evidence for a causative role of mast cells in small bowel polyposis, and related specific phenotypes and distributions of tumor infiltrating mast cells to stages of tumor growth. Here we report that, stabilization of ß-catenin expands mast cells to promote high incidence of colon polyposis and infrequent small bowel polyps and skin cancer. Expression of a dominant acting ß-catenin in mast cells (5CreCAT) stimulated maturation and expression of granule stored proteases. Both mucosal and connective tissue type mast cells accumulated in colonic small bowel polyps independent of gender, and mice developed chronic systemic inflammation with splenomegaly. Reconstitution of polyposis-prone mice with bone marrow from 5CreCAT mice resulted in focal expansion of connective tissue like mast cells, which are normally rare in benign polyps and characteristically expand during adenoma-to-carcinoma transition. Our findings highlight a hitherto unknown contribution of ß-catenin signaling in mast cells to their maturation and to increased risk of colon cancer.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Saadalla A,Lima MM,Tsai F,Osman A,Singh MP,Linden DR,Dennis KL,Haeryfar SMM,Gurish MF,Gounari F,Khazaie Kdoi
10.3389/fimmu.2019.02777subject
Has Abstractpub_date
2019-12-03 00:00:00pages
2777issn
1664-3224journal_volume
10pub_type
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pub_type: 传,历史文章,杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.3389/fimmu.2013.00225
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00421
更新日期:2016-10-17 00:00:00
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journal_title:Frontiers in immunology
pub_type: 已发布勘误
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