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Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice

Author:
Yan Lin, Lana C. DeMars
Source:
Plos One 2014 v.9 no.10 pp. 1-9
ISSN:
1932-6203
Subject:
chemokines, enzyme inhibitors, high fat diet, insulin, leptin, lung neoplasms, metastasis, mice, plasminogen activator, tumor necrosis factor-alpha, vascular endothelial growth factors
Abstract:
We investigated the effects of plasminogen activator inhibitor-1 (PAI-1) deficiency on spontaneous metastasis of Lewis lung carcinoma (LLC) in PAI-1 deficient (PAI-1-/-) and wildtype mice (C57BL/6J background) fed the AIN93G diet or that diet modified with 45% calories from fat. 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 of PAI-1 reduced the number of metastases by 35% (p < 0.01) compared to wildtype mice. In mice fed the high-fat diet, PIA-1 deficiency reduced tumor cross-sectional area by 52% (p < 0.05) and tumor volume by 61% (p < 0.05) compared to their wildtype counterparts; but PAI-1 deficiency had no significant effects on mice fed the AIN93G diet. Adipose and plasma concentrations of PAI-1 were significantly higher in high-fat fed wildtype mice than in their AIN93G-fed counterparts; they were not detectable in PAI-1-/- mice regardless of the diet. Conditioned medium from LLC cells was found to contain 32.7 ng PAI-1/mg protein. Furthermore, PAI-1 deficient mice showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-a, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wildtype mice. Those findings suggest that PAI-1 produced by the host promotes high-fat enhanced LLC progression and that compensatory overproduction of inflammatory cytokines and angiogenic factors may support LLC progression in the absence of PAI-1.
Agid:
59942
Handle:
10113/59942