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An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice.

ABSTRACT: Mast cells have been shown to release extracellular vesicles (EVs) in vitro. However, EV-mediated mast cell communication in vivo remains unexplored. Primary mast cells from GFP-transgenic and wild type mice, were grown in the presence or absence of lipopolysaccharide (LPS), and the secreted EVs were separated from the conditioned media. Mast cell-derived EVs were next cultured with LPS-naïve mast cells, and the induction of TNF-? expression was monitored. In addition, primary mast cells were seeded in diffusion chambers that were implanted into the peritoneal cavities of mice. Diffusion chambers enabled the release of GFP⁺ mast cell-derived EVs in vivo into the peritoneal cavity. Peritoneal lavage cells were assessed for the uptake of GFP⁺ EVs and for TNF-? production. In vitro, LPS-stimulated mast cell-derived EVs were efficiently taken up by non-stimulated mast cells, and induced TNF-? expression in a TLR4, JNK and P38 MAPK dependent manner. In vivo, using implanted diffusion chambers, we confirmed the release and transmission of mast cell-derived EVs to other mast cells with subsequent induction of TNF-? expression. These data show an EV-mediated spreading of pro-inflammatory response between mast cells, and provide the first in vivo evidence for the biological role of mast cell-derived EVs.

SUBMITTER: Vukman KV

PROVIDER: S-EPMC7890545 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice.

Vukman Krisztina V KV Ferencz Andrea A Fehér Daniella D Juhos Krisztina K Lőrincz Péter P Visnovitz Tamás T Koncz Anna A Pálóczi Krisztina K Seregélyes Gábor G Försönits András A Khamari Delaram D Galinsoga Alicia A Drahos László L Buzás Edit I EI

Journal of extracellular vesicles 20201101 1

Mast cells have been shown to release extracellular vesicles (EVs) in vitro. However, EV-mediated mast cell communication in vivo remains unexplored. Primary mast cells from GFP-transgenic and wild type mice, were grown in the presence or absence of lipopolysaccharide (LPS), and the secreted EVs were separated from the conditioned media. Mast cell-derived EVs were next cultured with LPS-naïve mast cells, and the induction of TNF-α expression was monitored. In addition, primary mast cells were se ...[more]

PMID: 33708356

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Project description:Advances in our understanding of cancer biology have contributed to generating different treatments to improve the survival of cancer patients. However, although initially most of the therapies are effective, relapse and recurrence occur in a large percentage of these cases after the treatment, and patients then die subsequently due to the development of therapy resistance in residual cancer cells. A large spectrum of molecular and cellular mechanisms have been identified as important contributors to therapy resistance, and more recently the inflammatory tumor microenvironment (TME) has been ascribed an important function as a source of signals generated by the TME that modulate cellular processes in the tumor cells, such as to favor the acquisition of therapy resistance. Currently, extracellular vesicles (EVs) are considered one of the main means of communication between cells of the TME and have emerged as crucial modulators of cancer drug resistance. Important in this context is, also, the inflammatory TME that can be caused by several conditions, including hypoxia and following chemotherapy, among others. These inflammatory conditions modulate the release and composition of EVs within the TME, which in turn alters the responses of the tumor cells to cancer therapies. The TME has been ascribed an important function as a source of signals that modulate cellular processes in the tumor cells, such as to favor the acquisition of therapy resistance. Although generally the main cellular components considered to participate in generating a pro-inflammatory TME are from the immune system (for instance, macrophages), more recently other types of cells of the TME have also been shown to participate in this process, including adipocytes, cancer-associated fibroblasts, endothelial cells, cancer stem cells, as well as the tumor cells. In this review, we focus on summarizing available information relating to the impact of a pro-inflammatory tumor microenvironment on the release of EVs derived from both cancer cells and cells of the TME, and how these EVs contribute to resistance to cancer therapies.

Dataset Information

An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice.

Publications

An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice.

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