Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in individuals with obesity. Here, we showed that macrophages accumulated within tumors of patients with obesity and CRC and in obese CRC mice and that they promoted accelerated tumor growth. These changes were initiated by oleic acid accumulation and subsequent tumor cell–derived acid production and were driven by macrophage signaling through the acid-sensing receptor GPR65. We found a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in patients with obesity and CRC or HCC also exhibited increased GPR65 expression, suggesting that the mechanism revealed here may contribute to tumor growth in a range of obesity-associated cancers and represent a potential therapeutic target.

中文翻译：

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肿瘤巨噬细胞上的酸敏感受体 GPR65 驱动肥胖患者的肿瘤生长


多种癌症，包括结直肠癌 （CRC），在肥胖个体中更常见，而且通常更具侵袭性。在这里，我们表明巨噬细胞在肥胖和 CRC 患者和肥胖 CRC 小鼠的肿瘤内积累，并且它们促进了肿瘤的加速生长。这些变化是由油酸积累和随后的肿瘤细胞衍生的酸产生引发的，并由巨噬细胞通过酸感应受体 GPR65 的信号传导驱动。我们发现 GPR65 在肥胖小鼠肝细胞癌 （HCC） 中具有类似的作用。肥胖和 CRC 或 HCC 患者的肿瘤也表现出 GPR65 表达增加，这表明此处揭示的机制可能有助于一系列肥胖相关癌症的肿瘤生长，并代表潜在的治疗靶点。