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Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment

PURPOSE: Perineural invasion (PNI) by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT) may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control...

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Autores principales: Bakst, Richard L., Lee, Nancy, He, Shuangba, Chernichenko, Natalya, Chen, Chun-Hao, Linkov, Gary, Le, H. Carl, Koutcher, Jason, Vakiani, Efsevia, Wong, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386941/
https://www.ncbi.nlm.nih.gov/pubmed/22768171
http://dx.doi.org/10.1371/journal.pone.0039925
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author Bakst, Richard L.
Lee, Nancy
He, Shuangba
Chernichenko, Natalya
Chen, Chun-Hao
Linkov, Gary
Le, H. Carl
Koutcher, Jason
Vakiani, Efsevia
Wong, Richard J.
author_facet Bakst, Richard L.
Lee, Nancy
He, Shuangba
Chernichenko, Natalya
Chen, Chun-Hao
Linkov, Gary
Le, H. Carl
Koutcher, Jason
Vakiani, Efsevia
Wong, Richard J.
author_sort Bakst, Richard L.
collection PubMed
description PURPOSE: Perineural invasion (PNI) by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT) may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined. EXPERIMENTAL DESIGN: An in vitro co-culture system of dorsal root ganglia (DRG) and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer. RESULTS: Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF). A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer cells, significantly inhibited PNI and was associated with decreased GDNF secretion but intact DRG viability. Radiation of cancer cells alone, co-cultured with non-radiated nerves, inhibited PNI through predominantly compromised cancer cell viability. In a murine model of PNI, a single 8 Gy dose of radiation to the sciatic nerve prior to implantation of non-radiated cancer cells resulted in decreased GDNF expression, decreased PNI by imaging and histology, and preservation of sciatic nerve motor function. CONCLUSIONS: Radiation may impair PNI through not only direct effects on cancer cell viability, but also an independent interruption of paracrine mechanisms underlying PNI. RT modulation of the nerve microenvironment may decrease PNI, and hold significant therapeutic implications for RT dosing and field design for patients with cancers exhibiting PNI.
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spelling pubmed-33869412012-07-05 Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment Bakst, Richard L. Lee, Nancy He, Shuangba Chernichenko, Natalya Chen, Chun-Hao Linkov, Gary Le, H. Carl Koutcher, Jason Vakiani, Efsevia Wong, Richard J. PLoS One Research Article PURPOSE: Perineural invasion (PNI) by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT) may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined. EXPERIMENTAL DESIGN: An in vitro co-culture system of dorsal root ganglia (DRG) and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer. RESULTS: Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF). A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer cells, significantly inhibited PNI and was associated with decreased GDNF secretion but intact DRG viability. Radiation of cancer cells alone, co-cultured with non-radiated nerves, inhibited PNI through predominantly compromised cancer cell viability. In a murine model of PNI, a single 8 Gy dose of radiation to the sciatic nerve prior to implantation of non-radiated cancer cells resulted in decreased GDNF expression, decreased PNI by imaging and histology, and preservation of sciatic nerve motor function. CONCLUSIONS: Radiation may impair PNI through not only direct effects on cancer cell viability, but also an independent interruption of paracrine mechanisms underlying PNI. RT modulation of the nerve microenvironment may decrease PNI, and hold significant therapeutic implications for RT dosing and field design for patients with cancers exhibiting PNI. Public Library of Science 2012-06-29 /pmc/articles/PMC3386941/ /pubmed/22768171 http://dx.doi.org/10.1371/journal.pone.0039925 Text en Bakst et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bakst, Richard L.
Lee, Nancy
He, Shuangba
Chernichenko, Natalya
Chen, Chun-Hao
Linkov, Gary
Le, H. Carl
Koutcher, Jason
Vakiani, Efsevia
Wong, Richard J.
Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title_full Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title_fullStr Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title_full_unstemmed Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title_short Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment
title_sort radiation impairs perineural invasion by modulating the nerve microenvironment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386941/
https://www.ncbi.nlm.nih.gov/pubmed/22768171
http://dx.doi.org/10.1371/journal.pone.0039925
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