論文 - 詳細
| RRC ID | 85379 |
|---|---|
| 著者 | Hirooka E, Hattori R, Ikawa K, Kobayashi T, Matsuyama M, Igaki T, Ohsawa S. |
| タイトル | Macrophages promote tumor growth by phagocytosis-mediated cytokine amplification in Drosophila. |
| ジャーナル | Curr Biol |
| Abstract |
Macrophages in the tumor microenvironment have been suggested to play a key role in driving tumor progression, but the underlying mechanism remains unclear. Here, we show in Drosophila imaginal discs that the phagocytic activity of mature phagocytic plasmatocytes, a subtype of Drosophila macrophages, promotes the growth of malignant tumors composed of epithelial cells that express activated Ras in combination with a scribble (scrib) mutation, which impairs cell polarity (RasV12/scrib). Mechanistically, caspase activation in dying RasV12/scrib cells induces infiltration of mature phagocytic plasmatocytes into RasV12/scrib tumors via reactive oxygen species (ROS) production, forming a feedback loop that reinforces caspase activation. Once inside the tumors, these plasmatocytes phagocytose caspase-activated RasV12/scrib cells exhibiting phosphatidylserine (PS) on their surface, which in turn induces unpaired 3 (Upd3, a homolog of interleukin-6 [IL-6]) production by the mature phagocytic plasmatocytes through the Draper-mediated engulfment pathway. This triggers non-autonomous induction of upds gene expression in RasV12/scrib tumors, leading to JAK/STAT-mediated boosting of tumor growth. Our findings uncover a mechanism of non-autonomous tumor progression by the phagocytic activity of macrophages, reminiscent of the cytokine amplification mechanism observed in the mammalian immune response. |
| 巻・号 | 35(13) |
| ページ | 3209-3227.e6 |
| 公開日 | 2025-7-7 |
| DOI | 10.1016/j.cub.2025.05.068 |
| PII | S0960-9822(25)00684-0 |
| PMID | 40570847 |
| MeSH | Animals Cytokines* / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / physiology Macrophages* / metabolism Macrophages* / physiology Membrane Proteins Phagocytosis* Reactive Oxygen Species / metabolism Transcription Factors / genetics Transcription Factors / metabolism Tumor Microenvironment Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism |
| IF | 9.601 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 24 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | HMJ30231 HMJ02128 18247R-3 11804R-3 8091R-1 HMJ22732 7788R-1 DGRC#108420 |