PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development

Rumney, R. M.H., Coffelt, S. B. , Neale, T. A., Dhayade, S., Tozer, G. M. and Miller, G. (2017) PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development. PLoS ONE, 12(12), e0188591. (doi:10.1371/journal.pone.0188591) (PMID:29220404) (PMCID:PMC5722323)

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Abstract

CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth
Authors: Rumney, R. M.H., Coffelt, S. B., Neale, T. A., Dhayade, S., Tozer, G. M., and Miller, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Rumney et al.
First Published:First published in PLoS ONE 12(12):e0188591
Publisher Policy:Reproduced under a Creative Commons License

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