Oncolytic Herpes Simplex Virus Inhibits Pediatric Brain Tumor Migration and Invasion
作者： Julia V. Cockle , Anke Brüning-Richardson , Karen J. Scott , Jill Thompson , Timothy Kottke
DOI: 10.1016/J.OMTO.2017.04.002
关键词: Oncolytic virus 、 Cytotoxic T cell 、 Herpes simplex virus 、 Pathology 、 Live cell imaging 、 Biology 、 Cell culture 、 Glioma 、 Virus 、 Adenomatous polyposis coli
摘要: Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine (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 previously unreported mechanism of action: the inhibition migration invasion in pediatric brain tumors. We evaluated effect oncolytic herpes simplex virus 1716 (HSV1716) on pHGG DIPG both in vitro using 2D (scratch assay, live cell imaging) 3D (spheroid collagen) assays in vivo an orthotopic xenograft model invasion. HSV1716 inhibited lines. cells demonstrated reduced velocity changed morphology presence virus. altered cytoskeletal dynamics by stabilizing microtubules, inhibiting glycogen synthase kinase-3, preventing localized clustering adenomatous polyposis coli (APC) leading edge cells. treatment tumor infiltration mouse model. Our results demonstrate that targets indicates potential (OV) be used novel anti-invasive strategy for
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