title: Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice.
abstract: This study investigated the effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) in plasminogen activator inhibitor-1 deficient (PAI-1-/-) and wild-type mice. The high-fat diet increased the number of pulmonary metastases by 60% (p<0.01), tumor cross-sectional area by 82% (p<0.05) and tumor volume by 130% (p<0.05) compared to the AIN93G diet. Deficiency in PAI-1 reduced the number of metastases by 35% (p<0.01) compared to wild-type mice. In mice fed the high-fat diet, PAI-1 deficiency reduced tumor cross-sectional area by 52% (p<0.05) and tumor volume by 61% (p<0.05) compared to their wild-type counterparts; however, PAI-1 deficiency affected neither area nor volume in mice fed the AIN93G diet. Adipose and plasma concentrations of PAI-1 were significantly higher in high-fat fed wild-type mice than in their AIN93G-fed counterparts. Adipose and plasma PAI-1 were not detectable in PAI-1-/- mice regardless of the diet. Mice deficient in PAI-1 showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-α, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wild-type mice, indicating a compensatory overproduction of inflammatory cytokines, angiogenic factors and insulin in the absence of PAI-1. We conclude that PAI-1 produced by the host, including that by adipose tissue, promotes high-fat enhanced metastasis of LLC.
authors.affiliation: Grand Forks Human Nutrition Research Center, United States Department of Agriculture, Agricultural Research Service, Grand Forks, North Dakota, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Grand Forks Human Nutrition Research Center, United States Department of Agriculture, Agricultural Research Service, Grand Forks, North Dakota, United States of America.
authors.forename: Lana C
authors.initials: LC
authors.lastname: DeMars
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics; D058258:Serpin E2 / Q000097:blood* / Q000235:genetics
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D009363:Neoplasm Proteins; D058258:Serpin E2; C511869:Serpine2 protein, mouse