Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.
Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.
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DOI：
10.1016/j.celrep.2023.112582
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发表时间：
2023-06-27
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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转移前的生态位形成是肿瘤转移扩散过程中的关键步骤。原发肿瘤在未来转移部位启动宿主细胞的一种方式是由于血管的纯粹流动而使肿瘤来源的微粒脱落。然而，目前尚不清楚常驻免疫细胞对这些颗粒的摄取如何影响它们的表型和功能。在这里，我们表明，巨噬细胞摄取肿瘤来源的微粒会诱导快速的代谢和表型转换，其特征是线粒体质量和功能增强，氧化磷酸化增加，黏附分子上调，导致早期转移肺的运动性降低。这种重新编程事件依赖于通过mTORC1途径的信号，而不是mTORC2途径，并且是由摄取肿瘤来源的微粒诱导的。总之，这些数据支持一种机制，即摄取肿瘤来源的微粒诱导巨噬细胞重新编程，以塑造它们在早期转移肺中的命运和功能。Kersten等人。结果显示，摄取肿瘤来源的微粒可诱导早期转移肺中非肺泡炎性巨噬细胞的代谢和表型转换。这种依赖mTORC1的重编程事件，其特征是OXPHOS和ATP的产生增加，以及黏附分子的上调，决定了巨噬细胞在转移过程中的表型和功能。
Pre-metastatic niche formation is a critical step during the metastatic spread of cancer. One way by which primary tumors prime host cells at future metastatic sites is through the shedding of tumor-derived microparticles as a consequence of vascular sheer flow. However, it remains unclear how the uptake of such particles by resident immune cells affects their phenotype and function. Here, we show that ingestion of tumor-derived microparticles by macrophages induces a rapid metabolic and phenotypic switch that is characterized by enhanced mitochondrial mass and function, increased oxidative phosphorylation, and upregulation of adhesion molecules, resulting in reduced motility in the early metastatic lung. This reprogramming event is dependent on signaling through the mTORC1, but not the mTORC2, pathway and is induced by uptake of tumor-derived microparticles. Together, these data support a mechanism by which uptake of tumor-derived microparticles induces reprogramming of macrophages to shape their fate and function in the early metastatic lung. Kersten et al. show that ingestion of tumor-derived microparticles induces a metabolic and phenotypic switch in non-alveolar inflammatory macrophages in the early metastatic lung. This mTORC1-dependent reprogramming event, characterized by increased OXPHOS, ATP production, and upregulation of adhesion molecules, dictates macrophage phenotype and function during metastasis.
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影响因子：
29
作者：
Crewe C;Funcke JB;Li S;Joffin N;Gliniak CM;Ghaben AL;An YA;Sadek HA;Gordillo R;Akgul Y;Chen S;Samovski D;Fischer-Posovszky P;Kusminski CM;Klein S;Scherer PE
通讯作者：
Scherer PE
影响因子：
64.8
作者：
Headley MB;Bins A;Nip A;Roberts EW;Looney MR;Gerard A;Krummel MF
通讯作者：
Krummel MF
影响因子：
16.6
作者：
Hallowell RW;Collins SL;Craig JM;Zhang Y;Oh M;Illei PB;Chan-Li Y;Vigeland CL;Mitzner W;Scott AL;Powell JD;Horton MR
通讯作者：
Horton MR
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D