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白色脂肪组织中的内皮Notch1信号促进癌症恶病质

原文发布日期：2023-09-25

英文摘要：

摘要翻译：

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白色脂肪组织中的内皮Notch1信号促进癌症恶病质

Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia

原文发布日期：2023-09-25

英文摘要：

Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.

摘要翻译：

癌性消瘦是癌症患者发生并发症和死亡的主要原因之一，其表现为体重减轻。白脂肪组织（WAT）重构的特征包括脂质储存障碍、炎症反应和最终导致纤维化。细胞耗损通常由肿瘤分泌因子引发。考虑到白脂肪组织内连续的内皮细胞是接触循环因素的第一道防线，我们推测：内皮自身是否可能 orchestrate 细胞重构？本研究结果显示，在癌性消瘦前期，肿瘤促进远处 WAT 内皮细胞激活 Notch1 信号通路。持续的内皮 Notch1 信号诱导雄性小鼠中白脂肪组织发生耗损特性。抑制 Retinoic 酸信号足以阻止小鼠癌症消瘦模型中的白脂肪耗损。这些发现表明，肿瘤通过调节远方内皮细胞上的angiocrine 信号来调控 WAT 耗损。