Oncolytic herpes simplex virus inhibits paediatric high grade glioma and diffuse intrinsic pontine glioma migration and invasion: Mechanism and potential for clinical application

Julia V. Cockle, Elizabeth Ilett, Anke Bruning-Richardson, Karen Scott, Susan Picton, Susan C Short, Alan Melcher

Research output: Contribution to journalMeeting Abstract

Abstract

INTRODUCTION: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival, and new treatments that target brain tumour invasion are needed. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells, while stimulating an anti-tumour immune response, offers a novel approach. Here, we evaluate the effect of oncolytic herpes simplex virus (HSV) 1716 on the migratory behaviour of a panel of pHGG and DIPG cell lines. METHOD: Migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Cell viability was examined by FACS and WST-1 assays. Levels of acetylated tubulin and glycogen synthase kinase-3 (GSK3) were evaluated by Western blot. RESULTS: HSV (multiplicity of infection 10) resulted in blockade of both migration (24h) and invasion (72h) in all cell lines. No significant cytotoxicity was demonstrated at these time points. pHGG cells demonstrated reduced velocity, loss of polarity and altered morphology in the presence of HSV 1716. HSV 1716 treatment of pHGG cells increased expression of acetylated tubulin (associated with stable rather than dynamic microtubules) and substantially reduced expression of GSK3 (a key regulator of cell migration and microtubule Dynamics). CONCLUSION: Our results demonstrate that HSV 1716 can block migration and invasion of pHGG and DIPG cells in vitro, potentially through microtubule stabilisation and inhibition of GSK3. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG, not only as a cytotoxic and immunogenic treatment, but as an anti-invasive agent, improving outcome for this devastating disease.
LanguageEnglish
Pages16
Number of pages1
JournalNeuro-Oncology
Volume17
Issue numberS8
DOIs
Publication statusPublished - Nov 2015
Externally publishedYes
EventBritish Neuro-Oncology Society Annual Meeting: "Neuro-Oncology Across the Ages" - Childhood to Old Age - University of Nottingham, Nottingham, United Kingdom
Duration: 1 Jul 20153 Jul 2015
https://www.bnos.org.uk/bnos-2015-annual-meeting/ (Link to Conference Information)

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Oncolytic Viruses
Simplexvirus
Glioma
Pediatrics
Glycogen Synthase Kinase 3
Microtubules
Tubulin
Oncolytic Virotherapy
Cell Line
Neoplasms
Virus Diseases
Therapeutics
Brain Neoplasms
Cell Movement
Cell Survival
Collagen
Western Blotting

Cite this

@article{c50ad1fd6ad44edd8747f4f8d7da9a9f,
title = "Oncolytic herpes simplex virus inhibits paediatric high grade glioma and diffuse intrinsic pontine glioma migration and invasion: Mechanism and potential for clinical application",
abstract = "INTRODUCTION: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival, and new treatments that target brain tumour invasion are needed. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells, while stimulating an anti-tumour immune response, offers a novel approach. Here, we evaluate the effect of oncolytic herpes simplex virus (HSV) 1716 on the migratory behaviour of a panel of pHGG and DIPG cell lines. METHOD: Migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Cell viability was examined by FACS and WST-1 assays. Levels of acetylated tubulin and glycogen synthase kinase-3 (GSK3) were evaluated by Western blot. RESULTS: HSV (multiplicity of infection 10) resulted in blockade of both migration (24h) and invasion (72h) in all cell lines. No significant cytotoxicity was demonstrated at these time points. pHGG cells demonstrated reduced velocity, loss of polarity and altered morphology in the presence of HSV 1716. HSV 1716 treatment of pHGG cells increased expression of acetylated tubulin (associated with stable rather than dynamic microtubules) and substantially reduced expression of GSK3 (a key regulator of cell migration and microtubule Dynamics). CONCLUSION: Our results demonstrate that HSV 1716 can block migration and invasion of pHGG and DIPG cells in vitro, potentially through microtubule stabilisation and inhibition of GSK3. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG, not only as a cytotoxic and immunogenic treatment, but as an anti-invasive agent, improving outcome for this devastating disease.",
author = "Cockle, {Julia V.} and Elizabeth Ilett and Anke Bruning-Richardson and Karen Scott and Susan Picton and Short, {Susan C} and Alan Melcher",
year = "2015",
month = "11",
doi = "10.1093/neuonc/nov283.03",
language = "English",
volume = "17",
pages = "16",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "S8",

}

Oncolytic herpes simplex virus inhibits paediatric high grade glioma and diffuse intrinsic pontine glioma migration and invasion : Mechanism and potential for clinical application. / Cockle, Julia V.; Ilett, Elizabeth; Bruning-Richardson, Anke; Scott, Karen ; Picton, Susan; Short, Susan C; Melcher, Alan.

In: Neuro-Oncology, Vol. 17, No. S8, 11.2015, p. 16.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - Oncolytic herpes simplex virus inhibits paediatric high grade glioma and diffuse intrinsic pontine glioma migration and invasion

T2 - Neuro-Oncology

AU - Cockle, Julia V.

AU - Ilett, Elizabeth

AU - Bruning-Richardson, Anke

AU - Scott, Karen

AU - Picton, Susan

AU - Short, Susan C

AU - Melcher, Alan

PY - 2015/11

Y1 - 2015/11

N2 - INTRODUCTION: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival, and new treatments that target brain tumour invasion are needed. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells, while stimulating an anti-tumour immune response, offers a novel approach. Here, we evaluate the effect of oncolytic herpes simplex virus (HSV) 1716 on the migratory behaviour of a panel of pHGG and DIPG cell lines. METHOD: Migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Cell viability was examined by FACS and WST-1 assays. Levels of acetylated tubulin and glycogen synthase kinase-3 (GSK3) were evaluated by Western blot. RESULTS: HSV (multiplicity of infection 10) resulted in blockade of both migration (24h) and invasion (72h) in all cell lines. No significant cytotoxicity was demonstrated at these time points. pHGG cells demonstrated reduced velocity, loss of polarity and altered morphology in the presence of HSV 1716. HSV 1716 treatment of pHGG cells increased expression of acetylated tubulin (associated with stable rather than dynamic microtubules) and substantially reduced expression of GSK3 (a key regulator of cell migration and microtubule Dynamics). CONCLUSION: Our results demonstrate that HSV 1716 can block migration and invasion of pHGG and DIPG cells in vitro, potentially through microtubule stabilisation and inhibition of GSK3. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG, not only as a cytotoxic and immunogenic treatment, but as an anti-invasive agent, improving outcome for this devastating disease.

AB - INTRODUCTION: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival, and new treatments that target brain tumour invasion are needed. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells, while stimulating an anti-tumour immune response, offers a novel approach. Here, we evaluate the effect of oncolytic herpes simplex virus (HSV) 1716 on the migratory behaviour of a panel of pHGG and DIPG cell lines. METHOD: Migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Cell viability was examined by FACS and WST-1 assays. Levels of acetylated tubulin and glycogen synthase kinase-3 (GSK3) were evaluated by Western blot. RESULTS: HSV (multiplicity of infection 10) resulted in blockade of both migration (24h) and invasion (72h) in all cell lines. No significant cytotoxicity was demonstrated at these time points. pHGG cells demonstrated reduced velocity, loss of polarity and altered morphology in the presence of HSV 1716. HSV 1716 treatment of pHGG cells increased expression of acetylated tubulin (associated with stable rather than dynamic microtubules) and substantially reduced expression of GSK3 (a key regulator of cell migration and microtubule Dynamics). CONCLUSION: Our results demonstrate that HSV 1716 can block migration and invasion of pHGG and DIPG cells in vitro, potentially through microtubule stabilisation and inhibition of GSK3. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG, not only as a cytotoxic and immunogenic treatment, but as an anti-invasive agent, improving outcome for this devastating disease.

U2 - 10.1093/neuonc/nov283.03

DO - 10.1093/neuonc/nov283.03

M3 - Meeting Abstract

VL - 17

SP - 16

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - S8

ER -