Circulating tumor cells shed large extracellular vesicles in capillary bifurcations that activate endothelial and immune cells.

Autor:	Vrynas A; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Bazban-Shotorbani S; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Arfan S; Division of Molecular Pathology, The Institute of Cancer Research; London, SM2 5NG, United Kingdom., Satia K; Cancer Research UK National Biomarker Centre, University of Manchester; Manchester, M13 9PL, United Kingdom.; Cancer Research UK Lung Cancer Centre of Excellence; Manchester, M13 9PL, United Kingdom., Ashna M; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Zhang A; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Visan D; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Chen A; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom., Carter M; Cancer Research UK National Biomarker Centre, University of Manchester; Manchester, M13 9PL, United Kingdom.; Cancer Research UK Lung Cancer Centre of Excellence; Manchester, M13 9PL, United Kingdom.; Medical Oncology, Christie Hospital National Health Service (NHS) Foundation Trust; Manchester, M20 4BX, United Kingdom., Blackhall F; Cancer Research UK Lung Cancer Centre of Excellence; Manchester, M13 9PL, United Kingdom.; Medical Oncology, Christie Hospital National Health Service (NHS) Foundation Trust; Manchester, M20 4BX, United Kingdom.; The Division of Cancer Sciences, Faculty of Biology, Medicine, and Health, University of Manchester; Manchester, M13 9PL, United Kingdom., Simpson KL; Cancer Research UK National Biomarker Centre, University of Manchester; Manchester, M13 9PL, United Kingdom.; Cancer Research UK Lung Cancer Centre of Excellence; Manchester, M13 9PL, United Kingdom.; SCLC Biology Group, Cancer Research UK Manchester Institute, University of Manchester; Manchester, M20 4BX, United Kingdom., Dive C; Cancer Research UK National Biomarker Centre, University of Manchester; Manchester, M13 9PL, United Kingdom.; Cancer Research UK Lung Cancer Centre of Excellence; Manchester, M13 9PL, United Kingdom.; SCLC Biology Group, Cancer Research UK Manchester Institute, University of Manchester; Manchester, M20 4BX, United Kingdom., Huang P; Division of Molecular Pathology, The Institute of Cancer Research; London, SM2 5NG, United Kingdom.; Cancer Research UK Convergence Science Centre; London, SW7 2AZ, United Kingdom., Au SH; Department of Bioengineering, Imperial College London; London, SW7 2AZ, United Kingdom.; Cancer Research UK Convergence Science Centre; London, SW7 2AZ, United Kingdom.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Dec 18. Date of Electronic Publication: 2024 Dec 18.
DOI:	10.1101/2024.04.17.589880
Abstrakt:	Circulating tumor cells (CTCs) and their clusters are the drivers of metastasis, but we have an incomplete understanding of how they interact with capillary beds. Using microfluidic models mimicking human capillary bifurcations, we observed cell size- and bifurcation-dependent shedding of nuclei-free fragments by patient CTCs, CTC-derived explant cells and numerous cancer cell lines. Shedding reduced cell sizes up to 61%, facilitating their transit through bifurcations. We demonstrated that shed fragments were a novel subclass of large extracellular vesicles (LEVs), "shearosomes", that require shear stress for their biogenesis and whose proteome was associated with immune-related pathways. Shearosomes exhibited functions characteristic of previously identified EVs including cell-directed internalization by endothelial and immune cells, and intercellular communication abilities such as disruption of endothelial barrier integrity, polarization of monocytes into M2 tumor-promoting macrophages and interactions between endothelial and immune cells. Cumulatively, these findings suggest that CTCs shed shearosomes in capillary beds that drive key processes involved in the formation of pre-metastatic niches.
Databáze:	MEDLINE
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