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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...

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Autores principales: Nandi, Bisweswar, Pai, Christine, Huang, Qin, Prabhala, Rao H., Munshi, Nikhil C., Gold, Jason S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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.
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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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