title: High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer.
abstract: Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high-fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer.
authors.affiliation: Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. scowen@miis.edu.|Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. scowen@miis.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cowen
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. smclaughlin@hsc.wvu.edu.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: McLaughlin
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. ghobbs@stat.wvu.edu.|Department of Statistics, West Virginia University, Morgantown, WV 26506, USA. ghobbs@stat.wvu.edu.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hobbs
authors.affiliation: Department of Pathology, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. jcoad@hsc.wvu.edu.
authors.forename: James
authors.initials: J
authors.lastname: Coad
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. kamartin@hsc.wvu.edu.|Department of Neurobiology and Anatomy, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. kamartin@hsc.wvu.edu.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Martin
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. imolfert@hsc.wvu.edu.|Department of Human Performance and Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. imolfert@hsc.wvu.edu.
authors.forename: I Mark
authors.initials: IM
authors.lastname: Olfert
authors.affiliation: Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu.|Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Vona-Davis
keywords: angiogenesis; high-fat diet; inflammation; obesity; tumor progression