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.

单核细胞趋化蛋白-1 (MCP-1) 是一种具有致癌潜力的脂肪因子。然而，缺乏脂肪产生的 MCP-1 是否会导致乳腺癌的证据。我们在本研究中检验了脂肪产生的 MCP-1 有助于乳腺肿瘤发生的假设。在小鼠乳腺肿瘤病毒-多瘤病毒中 T 抗原 (MMTV-PyMT) 的乳腺癌模型中，喂养有或没有脂肪 MCP-1 敲除的小鼠 [指定为Mcp-1 ^−/−或野生型 (WT)]标准AIN93G饮食（16%的能量来自大豆油）或高脂肪饮食（HFD，45%的能量来自大豆油）。脂肪 MCP-1 敲除降低了脂肪组织中的Mcp-1表达和血浆中 MCP-1 的浓度。喂食 HFD 的Mcp-1 ^−/−小鼠体内脂肪含量低于 WT 小鼠。脂肪 MCP-1 敲除减弱了 HFD 增强的乳腺肿瘤发生，乳腺肿瘤体积较小就证明了这一点。此外，无论饮食如何， Mcp-1 ^-/-小鼠的肿瘤潜伏期都比 WT 小鼠更长，肿瘤重量更轻。当喂食 HFD 时，与 WT 小鼠相比， Mcp-1 ^−/−小鼠血浆中胰岛素、瘦素、抵抗素、血管内皮生长因子和肝生长因子的浓度较低。总之，脂肪 MCP-1 缺乏减弱了 HFD 增强的 MMTV-PyMT 乳腺肿瘤发生。这种减弱可归因于Mcp-1 ^−/−小鼠体内脂肪减少、胰岛素敏感性改善以及促肿瘤炎症细胞因子和血管生成因子的下调。 结论是，脂肪产生的 MCP-1 有助于 MMTV-PyMT 小鼠模型中的乳腺肿瘤发生。