Effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice

Authors: Yan, Lin; Demars, Lana

Submitted to: Clinical and Experimental Metastasis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2010
Publication Date: 12/1/2010
Citation: Yan, L., Demars, L.C. 2010. Effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Clinical and Experimental Metastasis. 27(8):581-590.

Interpretive Summary: Obesity is a risk factor for cancer, and it is associated with the poor prognosis and the poor disease outcome of cancer survivors. The present study assessed the effects of dietary fat on malignant spread in mice. Three-week old mice were fed the AIN-93G standard diet contained 7% fat or a 45% fat diet for seven weeks before they were subcutaneously injected 2.5 x 105 viable Lewis lung carcinoma cells into the lower dorsal region. The primary tumor was resected two weeks later and mice were maintained on their respective diets for additional two weeks before the termination. This procedure of surgical removal of the primary tumor made this model relevant to conditions commonly encountered in human cancer patients. Feeding mice the high-fat diet significantly increased body weight and abdominal adipose content compared to the AIN-93G standard diet. There was a 2-fold increase in the number of tumor nodules formed in the lungs in the high-fat diet-fed mice compared to the mice fed the standard diet, and this increase was accompanied with significant increases in plasma concentrations of biomarkers related to angiogenesis (blood vessel formation). Results from the present study demonstrated that the high-fat diet enhanced malignant spread of Lewis lung carcinoma in mice and increased plasma concentrations of angiogenic biomarkers in mice, suggesting the high-fat diet might enhance the metastasis by promoting angiogenic processes.

Technical Abstract: The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G standard diet or a 45% fat diet (kcal %) for seven weeks before they were subcutaneously injected with 2.5 x 105 viable cells into the lower dorsal region. The primary tumor was resected two weeks later, and mice were maintained on their respective diets for additional two weeks before the termination. Feeding mice the high-fat diet significantly increased body weight and abdominal adipose content compared to the AIN-93G standard diet. There was a 2-fold increase in the number of tumor nodules developed in the lungs in the high-fat diet-fed mice compared to the standard diet-fed mice (P<0.05). There were no significant differences in plasma concentrations of TIMP-1, IL-1ß, VEGF and MCP-1 in non-tumor bearing mice fed the standard diet or the high-fat diet (referred to as control baseline and high-fat diet baseline). There were 3-, 4-, 40- and 12-fold increase in plasma TIMP-1 (non-significant), IL-1ß (P<0.05), VEGF (P<0.05) and MCP-1 (P<0.05) in tumor-bearing mice fed the standard diet compared to the control baseline. Dietary supplementation with 45% fat further significantly increased these cytokines in tumor-bearing mice (P<0.05 for each comparison). Feeding mice (either tumor-bearing or non-tumor-bearing) the high-fat diet significantly increased plasma concentration of leptin and significantly decreased plasma adiponectin compared to the standard diet. Results of the present study demonstrated that the high-fat diet enhanced spontaneous metastasis of Lewis lung carcinoma in mice and that this aggressiveness was accompanied with significant increases in plasma.