Cancer cachexia is associated with many types of tumors and is characterized by a combination of anorexia, loss of body weight, catabolic alterations, and systemic inflammation. We developed a tumor model in Drosophila larvae that causies cachexia-like syndrome, and we found that cachectic larvae show reduced levels of the circulating steroid ecdysone (Ec). Artificially importing Ec in the tumor through the use of the EcI/Oatp74D importer aggravated cachexia, whereas feeding animals with Ec rescued cachectic defects. This suggests that a steroid sink induced by the tumor promotes catabolic alterations in healthy tissues. We found that Oatp33Eb, a member of the Oatp transporter family, is specifically induced in tumors promoting cachexia. The overexpression of Oatp33Eb in noncachectic tumors induced cachexia, whereas its inhibition in cachectic tumors restored circulating Ec and reversed cachectic alterations. Oatp transporters are induced in several types of hormone-dependent tumors, and this result suggests that a similar sink effect could modify hormonal balance in cachectic cancer patients.

癌症恶病质与多种类型的肿瘤有关，其特征是厌食、体重减轻、分解代谢改变和全身炎症。我们在果蝇中开发了肿瘤模型引起恶病质样综合征的幼虫，我们发现恶病质幼虫的循环类固醇蜕皮激素 (Ec) 水平降低。通过使用 EcI/Oatp74D 导入器在肿瘤中人工导入 Ec 加重了恶病质，而用 Ec 喂养动物可以挽救恶病质缺陷。这表明肿瘤诱导的类固醇吸收促进了健康组织的分解代谢改变。我们发现 Oatp33Eb 是 Oatp 转运蛋白家族的成员，在促进恶病质的肿瘤中被特异性诱导。Oatp33Eb 在非恶病质肿瘤中的过表达诱导恶病质，而其在恶病质肿瘤中的抑制恢复了循环 Ec 并逆转了恶病质改变。Oatp 转运蛋白在几种类型的激素依赖性肿瘤中被诱导，