Oncotarget

Research Papers:

Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

Lin Yan _ and Sneha Sundaram

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Oncotarget. 2016; 7:24792-24799. https://doi.org/10.18632/oncotarget.8364

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Abstract

Lin Yan1, Sneha Sundaram1

1U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, U.S.A.

Correspondence to:

Lin Yan, e-mail: lin.yan@ars.usda.gov.

Keywords: MCP-1, pro-inflammatory cytokine, metastasis, high-fat diet, mice

Received: December 02, 2015    Accepted: February 28, 2016    Published: March 25, 2016

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.


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