Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Abstract Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or a...

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Autores principales:	Pedro A. C. Costa, Walison N. Silva, Pedro H. D. M. Prazeres, Caroline C. Picoli, Gabriela D. A. Guardia, Alinne C. Costa, Mariana A. Oliveira, Pedro P. G. Guimarães, Ricardo Gonçalves, Mauro C. X. Pinto, Jaime H. Amorim, Vasco A. C. Azevedo, Rodrigo R. Resende, Remo C. Russo, Thiago M. Cunha, Pedro A. F. Galante, Akiva Mintz, Alexander Birbrair
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Sensory neurons Tumor microenvironment Melanoma Neuronal activity Chemogenetics Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3bc21826b70242beab95f440ca474ea2
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spelling	oai:doaj.org-article:3bc21826b70242beab95f440ca474ea22021-11-21T12:07:34ZChemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression10.1186/s40478-021-01273-92051-5960https://doaj.org/article/3bc21826b70242beab95f440ca474ea22021-11-01T00:00:00Zhttps://doi.org/10.1186/s40478-021-01273-9https://doaj.org/toc/2051-5960Abstract Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.Pedro A. C. CostaWalison N. SilvaPedro H. D. M. PrazeresCaroline C. PicoliGabriela D. A. GuardiaAlinne C. CostaMariana A. OliveiraPedro P. G. GuimarãesRicardo GonçalvesMauro C. X. PintoJaime H. AmorimVasco A. C. AzevedoRodrigo R. ResendeRemo C. RussoThiago M. CunhaPedro A. F. GalanteAkiva MintzAlexander BirbrairBMCarticleSensory neuronsTumor microenvironmentMelanomaNeuronal activityChemogeneticsNeurology. Diseases of the nervous systemRC346-429ENActa Neuropathologica Communications, Vol 9, Iss 1, Pp 1-41 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sensory neurons Tumor microenvironment Melanoma Neuronal activity Chemogenetics Neurology. Diseases of the nervous system RC346-429
spellingShingle	Sensory neurons Tumor microenvironment Melanoma Neuronal activity Chemogenetics Neurology. Diseases of the nervous system RC346-429 Pedro A. C. Costa Walison N. Silva Pedro H. D. M. Prazeres Caroline C. Picoli Gabriela D. A. Guardia Alinne C. Costa Mariana A. Oliveira Pedro P. G. Guimarães Ricardo Gonçalves Mauro C. X. Pinto Jaime H. Amorim Vasco A. C. Azevedo Rodrigo R. Resende Remo C. Russo Thiago M. Cunha Pedro A. F. Galante Akiva Mintz Alexander Birbrair Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
description	Abstract Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.
format	article
author	Pedro A. C. Costa Walison N. Silva Pedro H. D. M. Prazeres Caroline C. Picoli Gabriela D. A. Guardia Alinne C. Costa Mariana A. Oliveira Pedro P. G. Guimarães Ricardo Gonçalves Mauro C. X. Pinto Jaime H. Amorim Vasco A. C. Azevedo Rodrigo R. Resende Remo C. Russo Thiago M. Cunha Pedro A. F. Galante Akiva Mintz Alexander Birbrair
author_facet	Pedro A. C. Costa Walison N. Silva Pedro H. D. M. Prazeres Caroline C. Picoli Gabriela D. A. Guardia Alinne C. Costa Mariana A. Oliveira Pedro P. G. Guimarães Ricardo Gonçalves Mauro C. X. Pinto Jaime H. Amorim Vasco A. C. Azevedo Rodrigo R. Resende Remo C. Russo Thiago M. Cunha Pedro A. F. Galante Akiva Mintz Alexander Birbrair
author_sort	Pedro A. C. Costa
title	Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
title_short	Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
title_full	Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
title_fullStr	Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
title_full_unstemmed	Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
title_sort	chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3bc21826b70242beab95f440ca474ea2
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Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

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