High-fat Diet Enhances Mammary Tumorigenesis and Pulmonary Metastasis and Alters Inflammatory and Angiogenic Profiles in MMTV-PyMT Mice

Abstract

The MMTV-PyMT transgenic mouse model is commonly used to study luminal B subtype, which has a lower prevalence but a worse prognosis than luminal A subtype among patients with breast cancer. The objective of the present study was to determine whether an obesogenic, high-fat diet enhances primary tumorigenesis and pulmonary metastasis in female MMTV-PyMT mice. The high-fat diet slightly but significantly increased caloric intake and body fat mass compared to the AIN93G diet. The high-fat diet significantly increased primary mammary tumor progression by 59%, primary tumor weight by 60%, and the number of lung metastases by 147%. Compared to the AIN93G diet, the high-fat diet significantly increased the abundance of proinflammatory cytokines (e.g. leptin, monocyte chemotactic protein-1, plasminogen activator inhibitor-1, resistin, and tumor necrosis factor-α) and angiogenic factors (e.g. hepatocyte growth factor, tissue inhibitor of metalloproteinase inhibitor-1, and vascular endothelial growth factor) in plasma and mammary tumors. We conclude that the obesogenic high-fat diet enhances primary tumorigenesis and metastasis in MMTV-PyMT mice. This enhancement may be the result of increased proinflammation and angiogenesis signaling.