The chemokine receptor CCR6 facilitates the onset of mammary neoplasia in the MMTV-PyMT mouse model via recruitment of tumor-promoting macrophages

Molecular Cancer

Research

Sarah T. Boyle¹  Jessica W. Faulkner¹  Marina Kochetkova¹  Shaun R. McColl² 

[1] Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia;Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia;Centre for Molecular Pathology, University of Adelaide, Adelaide, South Australia, Australia;

关键词: Breast Cancer;    Mammary Gland;    Chemokine Receptor;    CCR6;    Transgenic Mouse Model;    Immune System;    Macrophages;   

DOI  :  10.1186/s12943-015-0394-1

 received in 2015-02-12, accepted in 2015-05-29,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe expression of the chemokine receptor CCR6 has been previously correlated with higher grades and stages of breast cancer and decreased relapse-free survival. Also, its cognate chemokine ligand CCL20 has been reported to induce proliferation of cultured human breast epithelial cells.MethodsTo establish if CCR6 plays a functional role in mammary tumorigenesis, a bigenic MMTV-PyMT CCR6-null mouse was generated and mammary tumor development was assessed. Levels of tumor-infiltrating immune cells within tumor-bearing mammary glands from MMTV-PyMT Ccr6WT and Ccr6−/− mice were also analyzed.ResultsDeletion of CCR6 delayed tumor onset, significantly reduced the extent of initial hyperplastic outgrowth, and decreased tumor incidence in PyMT transgenic mice. CCR6 was then shown to promote the recruitment of pro-tumorigenic macrophages to the tumor site, facilitating the onset of neoplasia.ConclusionsThis study delineated for the first time a role for CCR6 in the development of breast cancer, and demonstrated a critical function for this receptor in maintaining the pro-tumorigenic cancer microenvironment.

【 授权许可】

Unknown   
© Boyle et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.