Melanoma-derived extracellular vesicles skew neutrophils into a pro-tumor phenotype.

Autor: Guimarães-Bastos D; Laboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.; Laboratory of RedOx Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Frony AC; Laboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil., Barja-Fidalgo C; Laboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil., Moraes JA; Laboratory of RedOx Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2022 Mar; Vol. 111 (3), pp. 585-596. Date of Electronic Publication: 2021 May 27.
DOI: 10.1002/JLB.3A0120-050RR
Abstrakt: Evidence shows that tumor cells abundantly produce and release extracellular vesicles (EVs) that can interact with stromal cells and modulate their functions. In the tumor neighborhood, neutrophils can assume both antitumor and pro-tumor phenotypes, known as TAN-N1 and TAN-N2, respectively. Nevertheless, the contribution of tumor-derived EVs to the modulation of TAN phenotypes is still poorly understood. The effects of EVs produced by a metastatic human melanoma cell line (MV3) on the differentiation and functional changes in human neutrophils were investigated. Treatment with MV3-derived EVs induced neutrophil chemotaxis through a signaling pathway involving the CXCR2/PI3K-Akt axis, prolonged neutrophil life span, promoted formation of neutrophil extracellular traps with poor elastase activity, and increased reactive oxygen species production. In contrast, EVs also increased the expression of TAN-N2 molecular markers (such as ARG1, CXCR4, and VEGF) in neutrophils. They also impaired oxide nitric and peroxynitrite production and diminished cytotoxic activity against melanoma cells, inducing neutrophils into a pro-tumor profile. Remarkably, EV-stimulated neutrophils did not exhibit phagocytic activity. These data suggested that melanoma-derived EVs could activate neutrophils, allowing their migration toward the tumor microenvironment, and driving these cells to a pro-tumor/N2 polarization, thus contributing to tumor progression.
(©2021 Society for Leukocyte Biology.)
Databáze: MEDLINE
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