Adipose-specific Monocyte Chemotactic Protein-1 Deficiency Reduces Pulmonary Metastasis of Lewis Lung Carcinoma in Mice

Abstract

Monocyte chemotactic protein-1 (MCP1) is a potent adipokine. This study tested the hypothesis that adipose-produced MCP1 contributes to metastasis. In a spontaneous metastasis model of Lewis lung carcinoma (LLC), male adipose MCP1-deficient (Mcp1-/-) and wild-type (WT) mice were fed the AIN93G diet or a high-fat diet (HFD) for 11 weeks. Lung metastasis from a subcutaneous tumor was the primary endpoint. The adipose expression of MCP1 was lower in Mcp1-/- mice than in WT controls. The HFD increased the number of lung metastases in WT mice. The number of metastasis was significantly lower in the HFD-fed Mcp1-/- mice than in the HFD-fed WT mice. Compared to the WT mice, adipose MCP1 deficiency lowered plasma concentrations of insulin, proinflammatory adipokines (leptin, plasminogen activator inhibitor-1, and resistin), and angiogenic markers (vascular endothelial growth factor, hepatocyte growth factor, and angiopoietin-2). Adipose MCP1 deficiency attenuates HFD-enhanced pulmonary metastasis of LLC.