title: Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet.
abstract: Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer. This 2x2 experiment was designed to investigate effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing 16% and 45% of energy from corn oil, respectively. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of lung metastases compared to the AIN93G control diet. Deficiency in MCP-1 reduced lung metastases by 37% in high-fat diet-fed mice; it reduced metastatic cross-sectional area by 46% and volume by 69% compared to wild-type mice. Adipose and plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed wild-type mice than in their AIN93G-fed counterparts; they were not detectable in MCP-1 deficient mice regardless of diet. Plasma concentrations of plasminogen activator inhibitor-1, tumor necrosis factor-α, vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1 were significantly higher in MCP-1 deficient mice compared to wild-type mice. We conclude that adipose-produced MCP-1 contributes to high-fat diet-enhanced metastasis. While MCP-1 deficiency reduces metastasis, the elevation of pro-inflammatory cytokines and angiogenic factors in the absence of MCP-1 may support the metastatic development and growth of LLC in MCP-1 deficient mice.
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, U.S.A.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, U.S.A.
authors.forename: Sneha
authors.initials: S
authors.lastname: Sundaram
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000473:pathology; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000378:metabolism; D059305:Diet, High-Fat; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2
keywords: MCP-1; high-fat diet; metastasis; mice; pro-inflammatory cytokine