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Cancer Res. 2013 Oct 1;73(19):6080-93. doi: 10.1158/0008-5472.CAN-13-0926. Epub 2013 Aug 19.

Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis.

Author information

1
Authors' Affiliations: Developmental, Molecular, and Chemical Biology Department, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine; Molecular Oncology Research Institute and Medical Oncology and Department of Pathology, Tufts Medical Center, Boston, Massachusetts; and Departments of Medicine, Duke University, Durham, North Carolina.

Abstract

Obesity is one of the most important preventable causes of cancer and the most significant risk factor for breast cancer in postmenopausal women. Compared with lean women, obese women are more likely to be diagnosed with a larger, higher grade tumor, an increased incidence of lymph node metastases, and elevated risk of distant recurrence. However, the mechanisms connecting obesity to the pathogenesis of breast cancer are poorly defined. Here, we show that during obesity, adipocytes within human and mouse breast tissues recruit and activate macrophages through a previously uncharacterized CCL2/IL-1β/CXCL12 signaling pathway. Activated macrophages in turn promote stromal vascularization and angiogenesis even before the formation of cancer. Recapitulating these changes using a novel humanized breast cancer model was sufficient to promote angiogenesis and prime the microenvironment prior to neoplastic transformation for accelerated breast oncogenesis. These findings provide a mechanistic role for adipocytes and macrophages before carcinogenesis that may be critical for prevention and treatment of obesity-related cancer.

PMID:
23959857
PMCID:
PMC3824388
DOI:
10.1158/0008-5472.CAN-13-0926
[Indexed for MEDLINE]
Free PMC Article

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