Submitted to: Anticancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/2016
Publication Date: 12/1/2016
Publication URL: http://handle.nal.usda.gov/10113/63338
Citation: Sundaram, S., Yan, L. 2016. High-fat diet enhances mammary tumorigenesis and pulmonary metastasis and alters inflammatory and angiogenic profiles in MMTV-PyMT mice. Anticancer Research. 36(12):6279-6288.
Interpretive Summary: Obesity is a risk factor for breast cancer. Being obese at the time of diagnosis of breast cancer is positively associated with poor prognosis and a greater risk of developing recurrent or metastatic cancer. These devastating aspects of breast cancer directly affect the quality life and survival of cancer patients. Fat tissues produce cancer promoting chemicals called adipokines that are increased by obesity. We determined whether a high-fat diet affected breast tumor growth and metastasis to the lungs in a mouse model of mammary tumor that mimics human breast cancer. The high-fat diet, compared to the low-fat diet, significantly increased growth of mammary tumors and the number of metastases formed in the lungs. Furthermore, the high-fat diet increased expression of a number of adipokines in plasma and mammary tumors. We concluded that high-fat diet enhanced primary mammary tumorigenesis and lung metastasis in this model of breast cancer. This enhancement may be a result of the up-regulation of adipokine production by the high-fat diet. It indicates that this mouse model can be useful in studies of lifestyle changes and dietary modification in the prevention of breast cancer.
Technical Abstract: The MMTV-PyMT transgenic mouse model is commonly used to study luminal B breast cancer, which has a lower prevalence but a worse prognosis. 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 (45% of energy from soybean oil) slightly but significantly increased caloric intake and body fat mass compared to the AIN93G diet (16% energy from soybean oil). The high-fat diet significantly increased primary mammary tumor progression by 59%, primary tumor weight by 60% and number of lung metastases by 147%. Compared to the AIN93G diet, the high-fat diet significantly increased the amounts of proinflammatory cytokines (e.g. monocyte chemotactic protein-1, plasminogen activator inhibitor-1, tumor necrosis factor-a, leptin, resistin) and angiogenic factors (e.g. vascular endothelial growth factor, tissue inhibitor of metalloprotease inhibitor-1, hepatocyte growth factor) in plasma and mammary tumors. We conclude that the obesogenic, high-fat diet enhanced primary tumorigenesis and metastasis in MMTV-PyMT mice. This enhancement may be the result of up-regulation of proinflammatory processes and angiogenesis.