Macrophages promote the progression of premalignant mammary lesions to invasive cancer

作者：Carron Emily C; Homra Samuel; Rosenberg Jillian; Coffelt Seth B; Kittrell Frances; Zhang Yiqun; Creighton Chad J; Fuqua Suzanne A; Medina Daniel; Machado Heather L^*

来源：Oncotarget, 2017, 8(31): 50731-50746.

DOI：10.18632/oncotarget.14913

• inflammation
• macrophage
• early stage lesion
• breast cancer progression
• mammary

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.

• 出版日期2017-8-1