Adipose monocyte chemotactic protein-1 deficiency reduces high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice.

Monocyte chemotactic protein-1 (MCP-1) is an adipokine with demonstrated carcinogenic potential. However, there is a lack of evidence whether adipose-produced MCP-1 contributes to breast cancer. We tested the hypothesis that adipose-produced MCP-1 contributes to mammary tumorigenesis in this study. In a breast cancer model of mouse mammary tumor virus-polyomavirus middle T-antigen (MMTV-PyMT), mice with or without adipose MCP-1 knockout [designated as Mcp-1-/- or wild-type (WT)] were fed the standard AIN93G diet (16% of energy from soybean oil) or a high-fat diet (HFD, 45% of energy from soybean oil). Adipose MCP-1 knockout reduced Mcp-1 expression in adipose tissue and concentrations of MCP-1 in plasma. Mcp-1-/- mice fed the HFD had less body fat than their WT counterparts. Adipose MCP-1 knockout attenuated HFD-enhanced mammary tumorigenesis, evidenced by lower mammary tumor volume. Furthermore, Mcp-1-/- mice, regardless of diet, had a longer tumor latency and less tumor weight than WT mice. When fed the HFD, Mcp-1-/- mice, compared to WT mice, exhibited lower concentrations of insulin, leptin, resistin, vascular endothelial growth factor and hepatic growth factor in plasma. In summary, adipose MCP-1 deficiency attenuated HFD-enhanced MMTV-PyMT mammary tumorigenesis. This attenuation can be attributed to less body adiposity, improvement in insulin sensitivity and down-regulation in protumorigenic inflammation cytokines and angiogenic factors in Mcp-1-/- mice. It concludes that adipose-produced MCP-1 contributes to mammary tumorigenesis in the MMTV-PyMT mouse model. Published by Elsevier Inc.

Citation

Sneha Sundaram, Lin Yan. Adipose monocyte chemotactic protein-1 deficiency reduces high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. The Journal of nutritional biochemistry. 2020 Mar;77:108313

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PMID: 31837540

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