School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720.
Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2405860121. doi: 10.1073/pnas.2405860121. Epub 2024 Oct 11.
Tumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic "bloating" of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6-like oncokines that perturb renal water-transporting cells and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units.
肿瘤可诱导远处器官发生全身性紊乱，导致宿主发病率增加的生理变化。在果蝇癌症模型中，几十年来人们已经知道肿瘤会导致腹部过度充满液体的“肿胀”。在这里，我们使用同种异体移植和转基因肿瘤来表明，宿主表现出与果蝇肾小管自主分泌功能缺陷相关的液体潴留，这些肾小管的功能类似于人类肾脏。这些器官的排泄被异常细胞阻断，这些异常细胞来源于正常静止的肾干细胞（RSCs）的不当激活。阻断是由类似于 IL-6 的致癌因子引发的，这些因子扰乱了肾脏的水转运细胞，并在 RSCs 中引发病理性的损伤反应。因此，肿瘤产生的慢性炎症状态通过改变宿主肾单位的细胞内稳态引起副肿瘤性液体失调。
