Paraneoplastic renal dysfunction in fly cancer models driven by inflammatory activation of stem cells

• 成果类型: Article
• 署名作者: Kwok, Sze Hang; Liu, Yuejiang; Bilder, David; Kim, Jung
• 署名单位: University of Hong Kong; University of California System; University of California Berkeley
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9060
• DOI: 10.1073/pnas.2405860121
• 发表日期: 2024-10-15
• 关键词: malpighian tubules; drosophila; expression

摘要

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.