CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition

Neeraj Kapur; Hina Mir; Clarence E. Clark; Uma Krishnamurti; Derrick J. Beech; James W. Lillard; Shailesh Singh

doi:10.1038/bjc.2016.113

CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition

Neeraj Kapur, Hina Mir, Clarence E. Clark, Uma Krishnamurti, Derrick J. Beech, James W. Lillard, Shailesh Singh

Internal Medicine

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.

Original language	English
Pages (from-to)	1343-1351
Number of pages	9
Journal	British Journal of Cancer
Volume	114
Issue number	12
DOIs	https://doi.org/10.1038/bjc.2016.113
State	Published - Jun 14 2016

Bibliographical note

Funding Information:
This study was supported in part by the funds (R21 CA169716, SC1 CA180212, U54 CA118638 and UO1 CA179701) from NCI and Morehouse School of Medicine flow cytometry core (G12 MD007602).

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2016.113

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title = "CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition",

abstract = "Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.",

author = "Neeraj Kapur and Hina Mir and Clark, {Clarence E.} and Uma Krishnamurti and Beech, {Derrick J.} and Lillard, {James W.} and Shailesh Singh",

note = "Funding Information: This study was supported in part by the funds (R21 CA169716, SC1 CA180212, U54 CA118638 and UO1 CA179701) from NCI and Morehouse School of Medicine flow cytometry core (G12 MD007602).",

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doi = "10.1038/bjc.2016.113",

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AU - Kapur, Neeraj

AU - Mir, Hina

AU - Clark, Clarence E.

AU - Krishnamurti, Uma

AU - Beech, Derrick J.

AU - Lillard, James W.

AU - Singh, Shailesh

N1 - Funding Information: This study was supported in part by the funds (R21 CA169716, SC1 CA180212, U54 CA118638 and UO1 CA179701) from NCI and Morehouse School of Medicine flow cytometry core (G12 MD007602).

PY - 2016/6/14

Y1 - 2016/6/14

N2 - Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.

AB - Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.

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CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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