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Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis
M3 muscarinic receptor (M3R) activation promotes colon cancer cell proliferation, migration, and invasion in vitro. Although over-expression of CHRM3, the gene encoding M3R, is reported in primary colon cancers, expression of M3R itself has not been studied in colon neoplasia. We compared M3R expres...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400569/ https://www.ncbi.nlm.nih.gov/pubmed/28416748 http://dx.doi.org/10.18632/oncotarget.15500 |
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author | Cheng, Kunrong Shang, Aaron C. Drachenberg, Cinthia B. Zhan, Min Raufman, Jean-Pierre |
author_facet | Cheng, Kunrong Shang, Aaron C. Drachenberg, Cinthia B. Zhan, Min Raufman, Jean-Pierre |
author_sort | Cheng, Kunrong |
collection | PubMed |
description | M3 muscarinic receptor (M3R) activation promotes colon cancer cell proliferation, migration, and invasion in vitro. Although over-expression of CHRM3, the gene encoding M3R, is reported in primary colon cancers, expression of M3R itself has not been studied in colon neoplasia. We compared M3R expression in normal colon to colon adenomas, and primary and metastatic colon cancers. Compared to adjacent normal colon, CHRM3 expression was increased up to 128-fold in 10 of 18 consecutive surgical cancer specimens (56%) and associated with metastatic spread (P < 0.05). To analyze M3R protein expression we interrogated 29 consecutive paraffin-embedded colon adenocarcinomas and adjacent normal colon using a specific anti-M3R antibody and immunoperoxidase staining. This revealed weak M3R expression in normal colonocytes, primarily on basolateral surfaces. In contrast, in 25 of 29 cancer tissues (86%) we observed both cytoplasmic and plasma membrane over-expression of M3R; compared to normal epithelium, mean M3R staining intensity was increased more than two-fold in colon cancer (P < 0.001). M3R staining was also increased in 22 colon adenomas compared to adjacent normal colon (P < 0.001). In contrast, M3R staining intensity was not increased in lymph node or liver metastases. These findings suggest M3R expression plays an important role in early progression and invasion of colon neoplasia but is less important once tumors have spread. |
format | Online Article Text |
id | pubmed-5400569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54005692017-05-03 Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis Cheng, Kunrong Shang, Aaron C. Drachenberg, Cinthia B. Zhan, Min Raufman, Jean-Pierre Oncotarget Research Paper M3 muscarinic receptor (M3R) activation promotes colon cancer cell proliferation, migration, and invasion in vitro. Although over-expression of CHRM3, the gene encoding M3R, is reported in primary colon cancers, expression of M3R itself has not been studied in colon neoplasia. We compared M3R expression in normal colon to colon adenomas, and primary and metastatic colon cancers. Compared to adjacent normal colon, CHRM3 expression was increased up to 128-fold in 10 of 18 consecutive surgical cancer specimens (56%) and associated with metastatic spread (P < 0.05). To analyze M3R protein expression we interrogated 29 consecutive paraffin-embedded colon adenocarcinomas and adjacent normal colon using a specific anti-M3R antibody and immunoperoxidase staining. This revealed weak M3R expression in normal colonocytes, primarily on basolateral surfaces. In contrast, in 25 of 29 cancer tissues (86%) we observed both cytoplasmic and plasma membrane over-expression of M3R; compared to normal epithelium, mean M3R staining intensity was increased more than two-fold in colon cancer (P < 0.001). M3R staining was also increased in 22 colon adenomas compared to adjacent normal colon (P < 0.001). In contrast, M3R staining intensity was not increased in lymph node or liver metastases. These findings suggest M3R expression plays an important role in early progression and invasion of colon neoplasia but is less important once tumors have spread. Impact Journals LLC 2017-02-18 /pmc/articles/PMC5400569/ /pubmed/28416748 http://dx.doi.org/10.18632/oncotarget.15500 Text en Copyright: © 2017 Cheng et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Cheng, Kunrong Shang, Aaron C. Drachenberg, Cinthia B. Zhan, Min Raufman, Jean-Pierre Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title | Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title_full | Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title_fullStr | Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title_full_unstemmed | Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title_short | Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis |
title_sort | differential expression of m3 muscarinic receptors in progressive colon neoplasia and metastasis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400569/ https://www.ncbi.nlm.nih.gov/pubmed/28416748 http://dx.doi.org/10.18632/oncotarget.15500 |
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