Related Experiment Video
Updated: Mar 1, 2026
Establishment of Orthotopic Patient-derived Xenograft Models for Brain Tumors using a Stereotaxic Device
Published on: May 2, 2025
Oncolytic Herpes Simplex Virus Inhibits Pediatric Brain Tumor Migration and Invasion
Julia V Cockle1,2, Anke Brüning-Richardson1, Karen J Scott1
1Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
Abstract:
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion. HSV1716 inhibited migration and invasion in pHGG and DIPG cell lines. pHGG cells demonstrated reduced velocity and changed morphology in the presence of virus. HSV1716 altered pHGG cytoskeletal dynamics by stabilizing microtubules, inhibiting glycogen synthase kinase-3, and preventing localized clustering of adenomatous polyposis coli (APC) to the leading edge of cells. HSV1716 treatment also reduced tumor infiltration in a mouse orthotopic xenograft DIPG model. Our results demonstrate that HSV1716 targets the migration and invasion of pHGG and DIPG and indicates the potential of an oncolytic virus (OV) to be used as a novel anti-invasive treatment strategy for pediatric brain tumors.
Insights
Oncolytic herpes simplex virus 1716 (HSV1716) effectively inhibits the migration and invasion of pediatric brain tumors like high-grade glioma and diffuse intrinsic pontine glioma. This oncolytic virus shows potential as a novel anti-invasive therapy for these aggressive pediatric cancers.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are aggressive brain tumors with limited treatment options and poor prognoses.
- Oncolytic virotherapy, using viruses to target cancer cells, is evolving beyond direct cytotoxicity to include immune-mediated and anti-invasive mechanisms.
- Understanding novel mechanisms of action for oncolytic viruses is crucial for developing more effective pediatric brain tumor therapies.
Purpose of the Study:
- To investigate the previously unreported anti-invasive effects of oncolytic herpes simplex virus 1716 (HSV1716) on pediatric brain tumors.
- To evaluate the impact of HSV1716 on the migration and invasion capabilities of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) cell lines.
- To explore the molecular mechanisms by which HSV1716 inhibits tumor cell movement and invasion.
Main Methods:
- In vitro studies utilized 2D assays (scratch assay, live cell imaging) and 3D spheroid invasion assays in collagen to assess HSV1716's effect on pHGG and DIPG cell migration and invasion.
- In vivo efficacy was evaluated using an orthotopic xenograft mouse model of DIPG invasion.
- Mechanistic studies investigated HSV1716's impact on cytoskeletal dynamics, including microtubule stability and key signaling pathways like glycogen synthase kinase-3 (GSK-3) and adenomatous polyposis coli (APC) clustering.
Main Results:
- HSV1716 significantly inhibited both migration and invasion in pHGG and DIPG cell lines.
- pHGG cells treated with HSV1716 exhibited reduced migration velocity and altered cell morphology.
- HSV1716 was found to stabilize microtubules, inhibit GSK-3, and prevent APC clustering at the leading edge of migrating cells, thereby altering cytoskeletal dynamics. Tumor infiltration was also reduced in the in vivo DIPG model.
Conclusions:
- Oncolytic herpes simplex virus 1716 (HSV1716) demonstrates a potent anti-migratory and anti-invasive effect against pediatric high-grade glioma and diffuse intrinsic pontine glioma.
- HSV1716's mechanism involves the modulation of cytoskeletal dynamics, offering a new therapeutic avenue.
- These findings highlight the potential of oncolytic viruses as a novel strategy for anti-invasive treatment in pediatric brain tumors.
