Abstract 1824: Effects of high-fat diet feeding on solid tumor growth and lung metastasis in the Lewis lung cancer allograft model

Abstract

Abstract Epidemiological studies indicate that overweight and obesity are associated with increased risk of developing several cancers. In the present study, we determined whether a chronic consumption of a high-fat diet increases solid tumor growth and metastasis in the C57BL/6N mouse lung cancer allograft model. Four-week old, male C57BL/6N mice were fed a purified diet containing 34.9% (w/w) fat (high fat diet) or 4.3 % fat (control diet) for 16 weeks, and then Lewis lung carcinoma cells were subcutaneously injected at 5 × 104 cells per mouse into the animals’ left flank. The primary tumor was resected 3 weeks later, and all animals were killed 21 days after the surgery. The high-fat diet feeding significantly increased the body weights and energy intakes as compared with those in the control diet group. The weights of the liver, spleen, epididymal fat pad, and mesenteric fat pad were increased in the high-fat diet group compared to the control group. The high fat diet increased solid tumor growth as well as the number and the size of colonies in the lung. Immunohistochemical staining of tumor tissues revealed that the expression of Ki67 (prototypic cell cycle related nuclear antigen), CD45 (phospho-tyrosine phosphatase), CD31 (platelet endothelial cell adhesion molecule-1), vascular endothelial growth factor (VEGF), cyclin-dependent kinase 4, cyclin A, and cyclin D1 was significantly increased in the high-fat diet group compared to the control group. The high-fat diet feeding significantly increased the blood levels of leptin, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), granulocyte-colony stimulating factor (G-CSF), triggering receptor expressed on myeloid cells-1 (TREM-1), angiopoietin-1 (Ang-1), chemokine ligand 16 (CXCL16), plasminogen activator inhibitor-1 (PAI-1), and stromal cell-derived factor-1 (SDF-1) compared to the control group. Results of the present study indicate that the prolonged consumption of a high-fat diet enhances the secretion of cytokines, chemokines, matrix metalloproteinases, and angiogenesis-related proteins and increases the infiltration of macrophages into tumor tissues which, in turn, stimulate the proliferation and metastasis of lung cancer cells. The increased angiogenesis probably contributes to increased tumor growth and metastasis in mice fed on a high-fat diet. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1824. doi:10.1158/1538-7445.AM2011-1824