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Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons

Solid tumors are complex collections of cells surrounded by benign tissues that influence and are influenced by the tumor. These surrounding cells include vasculature, immune cells, neurons, and other cell types, and are collectively known as the tumor microenvironment. Tumors manipulate their micro...

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Autores principales: Hunt, Patrick J., Amit, Moran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861575/
https://www.ncbi.nlm.nih.gov/pubmed/33554224
http://dx.doi.org/10.20517/evcna.2020.04
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author Hunt, Patrick J.
Amit, Moran
author_facet Hunt, Patrick J.
Amit, Moran
author_sort Hunt, Patrick J.
collection PubMed
description Solid tumors are complex collections of cells surrounded by benign tissues that influence and are influenced by the tumor. These surrounding cells include vasculature, immune cells, neurons, and other cell types, and are collectively known as the tumor microenvironment. Tumors manipulate their microenvironment for the benefit of the tumor. Autonomic neurons innervate and drive malignant growth in a variety of solid tumors. However, the mechanisms underlying neuron-tumor relationships are not well understood. Recently, Amit et al. described that trophic relationships between oral cavity squamous cell carcinomas (OCSCCs) and nearby autonomic neurons arise through direct signaling between tumors and local neurons. An inducible tumor model in which 4NQO was introduced into the drinking water of Trp53 knockout mice was used to model OCSCC-microenvironment interactions. Using this model, this group discovered that loss of p53 expression in OCSCC tumors resulted in increased nerve density within these tumors. This neuritogenesis was controlled by tumor-derived microRNA-laden extracellular vesicles (EVs). Specifically, EV-delivered miR-34a inhibited neuritogenesis, whereas EV-delivered miR-21 and miR-324 increased neuritogenesis. The neurons innervating p53-deficient OCSCC tumors were predominantly adrenergic and arose through the transdifferentiation of trigeminal sensory nerve fibers to adrenergic nerve fibers. This transdifferentiation corresponded with increased expression of neuron-reprogramming transcription factors, including POU5F1, KLF4, and ASCL1, which were overexpressed in the p53-deficient samples, and are proposed targets of miR-34a-mediated regulation. Human OCSCC samples enriched in adrenergic neuron markers are associated strongly with poor outcomes, thus demonstrating the relevance of these findings to cancer patients.
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spelling pubmed-78615752021-02-04 Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons Hunt, Patrick J. Amit, Moran Extracell Vesicles Circ Nucl Acids Article Solid tumors are complex collections of cells surrounded by benign tissues that influence and are influenced by the tumor. These surrounding cells include vasculature, immune cells, neurons, and other cell types, and are collectively known as the tumor microenvironment. Tumors manipulate their microenvironment for the benefit of the tumor. Autonomic neurons innervate and drive malignant growth in a variety of solid tumors. However, the mechanisms underlying neuron-tumor relationships are not well understood. Recently, Amit et al. described that trophic relationships between oral cavity squamous cell carcinomas (OCSCCs) and nearby autonomic neurons arise through direct signaling between tumors and local neurons. An inducible tumor model in which 4NQO was introduced into the drinking water of Trp53 knockout mice was used to model OCSCC-microenvironment interactions. Using this model, this group discovered that loss of p53 expression in OCSCC tumors resulted in increased nerve density within these tumors. This neuritogenesis was controlled by tumor-derived microRNA-laden extracellular vesicles (EVs). Specifically, EV-delivered miR-34a inhibited neuritogenesis, whereas EV-delivered miR-21 and miR-324 increased neuritogenesis. The neurons innervating p53-deficient OCSCC tumors were predominantly adrenergic and arose through the transdifferentiation of trigeminal sensory nerve fibers to adrenergic nerve fibers. This transdifferentiation corresponded with increased expression of neuron-reprogramming transcription factors, including POU5F1, KLF4, and ASCL1, which were overexpressed in the p53-deficient samples, and are proposed targets of miR-34a-mediated regulation. Human OCSCC samples enriched in adrenergic neuron markers are associated strongly with poor outcomes, thus demonstrating the relevance of these findings to cancer patients. 2020-12-30 2020 /pmc/articles/PMC7861575/ /pubmed/33554224 http://dx.doi.org/10.20517/evcna.2020.04 Text en This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Hunt, Patrick J.
Amit, Moran
Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title_full Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title_fullStr Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title_full_unstemmed Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title_short Head and neck cancer exosomes drive microRNA-mediated reprogramming of local neurons
title_sort head and neck cancer exosomes drive microrna-mediated reprogramming of local neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861575/
https://www.ncbi.nlm.nih.gov/pubmed/33554224
http://dx.doi.org/10.20517/evcna.2020.04
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