Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.

Autor:	Kersten K; Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California San Francisco, San Francisco, CA 94143, USA., You R; Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California San Francisco, San Francisco, CA 94143, USA., Liang S; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA., Tharp KM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA., Pollack J; ImmunoX Initiative, University of California San Francisco, San Francisco, CA 94143, USA; Foundery Innovations, San Francisco, CA 94080, USA., Weaver VM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA., Krummel MF; Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California San Francisco, San Francisco, CA 94143, USA; Foundery Innovations, San Francisco, CA 94080, USA., Headley MB; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA. Electronic address: mheadley@fredhutch.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jun 27; Vol. 42 (6), pp. 112582. Date of Electronic Publication: 2023 May 31.
DOI:	10.1016/j.celrep.2023.112582
Abstrakt:	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. Competing Interests: Declaration of interests M.F.K. is a founder and shareholder in Foundery Innovations that prosecutes and develops novel immunotherapeutics, respectively. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu