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CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis
Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035256/ https://www.ncbi.nlm.nih.gov/pubmed/24866282 http://dx.doi.org/10.1371/journal.pone.0097566 |
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author | Nandi, Bisweswar Pai, Christine Huang, Qin Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. |
author_facet | Nandi, Bisweswar Pai, Christine Huang, Qin Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. |
author_sort | Nandi, Bisweswar |
collection | PubMed |
description | Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APC(MIN/+) mice) to generate APC(MIN/+) mice with CCR6 knocked out (CCR6KO-APC(MIN/+) mice). CCR6KO-APC(MIN/+) mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APC(MIN/+) also had normal sized spleens as compared to the enlarged spleens found in APC(MIN/+) mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APC(MIN/+) as compared to APC(MIN/+) mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy. |
format | Online Article Text |
id | pubmed-4035256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40352562014-06-02 CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis Nandi, Bisweswar Pai, Christine Huang, Qin Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. PLoS One Research Article Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APC(MIN/+) mice) to generate APC(MIN/+) mice with CCR6 knocked out (CCR6KO-APC(MIN/+) mice). CCR6KO-APC(MIN/+) mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APC(MIN/+) also had normal sized spleens as compared to the enlarged spleens found in APC(MIN/+) mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APC(MIN/+) as compared to APC(MIN/+) mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy. Public Library of Science 2014-05-27 /pmc/articles/PMC4035256/ /pubmed/24866282 http://dx.doi.org/10.1371/journal.pone.0097566 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Nandi, Bisweswar Pai, Christine Huang, Qin Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title | CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title_full | CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title_fullStr | CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title_full_unstemmed | CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title_short | CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis |
title_sort | ccr6, the sole receptor for the chemokine ccl20, promotes spontaneous intestinal tumorigenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035256/ https://www.ncbi.nlm.nih.gov/pubmed/24866282 http://dx.doi.org/10.1371/journal.pone.0097566 |
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