Macrophages promote the progression of premalignant mammary lesions to invasive cancer.

Carron, E. C., Homra, S., Rosenberg, J., Coffelt, S. B. , Kittrell, F., Zhang, Y., Creighton, C. J., Fuqua, S. A., Medina, D. and Machado, H. L. (2017) Macrophages promote the progression of premalignant mammary lesions to invasive cancer. Oncotarget, 8(31), pp. 50731-50746. (doi: 10.18632/oncotarget.14913) (PMID:28159924)

Abstract

Breast cancer initiation, progression and metastasis rely on a complex interplay between tumor cells and their surrounding microenvironment. Infiltrating immune cells, including macrophages, promote mammary tumor progression and metastasis; however, less is known about the role of macrophages in early stage lesions. In this study, we utilized a transplantable p53-null model of early progression to characterize the immune cell components of early stage lesions. We show that macrophages are recruited to ductal hyperplasias with a high tumor-forming potential where they are differentiated and polarized toward a tumor-promoting phenotype. These macrophages are a unique subset of macrophages, characterized by pro-inflammatory, anti-inflammatory and immunosuppressive factors. Macrophage ablation studies showed that macrophages are required for both early stage progression and primary tumor formation. These studies suggest that therapeutic targeting of tumor-promoting macrophages may not only be an effective strategy to block tumor progression and metastasis, but may also have critical implications for breast cancer prevention.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Coffelt, Professor Seth
• Authors: Carron, E. C., Homra, S., Rosenberg, J., Coffelt, S. B., Kittrell, F., Zhang, Y., Creighton, C. J., Fuqua, S. A., Medina, D., and Machado, H. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncotarget
• Publisher: Impact Journals
• ISSN: 1949-2553
• ISSN (Online): 1949-2553
• Published Online: 31 January 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Oncotarget 8(31): 50731-50746
• Publisher Policy: Reproduced under a Creative Commons License