Human pontine glioma cells can induce murine tumor

Authors: Viola Caretti A Charlotte P Sewing Tonny Lagerweij Pepijn Schellen Marianna Bugiani Marc H A Jansen Dannis G van Vuurden Anna C Navis Ilona Horsman W Peter Vandertop David P Noske Pieter Wesseling Gertjan J L Kaspers Javad Nazarian Hannes Vogel Esther Hulleman Michelle Monje Thomas Wurdinger

Publish Date: 2014/04/29

Volume: 127, Issue: 6, Pages: 897-909

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Abstract

Diffuse intrinsic pontine glioma DIPG with a median survival of only 9 months is the leading cause of pediatric brain cancer mortality Dearth of tumor tissue for research has limited progress in this disease until recently New experimental models for DIPG research are now emerging To develop preclinical models of DIPG two different methods were adopted cells obtained at autopsy 1 were directly xenografted orthotopically into the pons of immunodeficient mice without an intervening cell culture step or 2 were first cultured in vitro and upon successful expansion injected in vivo Both strategies resulted in pontine tumors histopathologically similar to the original human DIPG tumors However following the direct transplantation method all tumors proved to be composed of murine and not of human cells This is in contrast to the indirect method that included initial in vitro culture and resulted in xenografts comprising human cells Of note direct injection of cells obtained postmortem from the pons and frontal lobe of human brains not affected by cancer did not give rise to neoplasms The murine pontine tumors exhibited an immunophenotype similar to human DIPG but were also positive for microglia/macrophage markers such as CD45 CD68 and CD11b Serial orthotopic injection of these murine cells results in lethal tumors in recipient mice Direct injection of human DIPG cells in vivo can give rise to malignant murine tumors This represents an important caveat for xenotransplantation models of DIPG In contrast an initial in vitro culture step can allow establishment of human orthotopic xenografts The mechanism underlying this phenomenon observed with direct xenotransplantation remains an open questionWe would like to thank the patients and families who so generously donated tissue for this research We sincerely thank the architect and artist Alessandra Luoni for drawing Fig 1a We gracefully acknowledge Alyssa Noll Departments of Neurology and Pediatrics for support with animal experiments and Patty Lovelace FACS Core for her expertise with flow cytometry experiments all from Stanford USA The flow cytometer used was purchased using an NIH S10 Shared Instrumentation Grant 1S10RR02933801 We are thankful to Jacqueline Cloos Department of Pediatric Oncology VU University Medical Center The Netherlands and Dana Bangs Cytogenetics Laboratory Stanford USA for their mastery in analyzing metaphase spreads We are also thankful to Sridevi Yadavilli for processing postmortem specimens and assisting in murine injections Research Center for Genetic Medicine Children’s National Medical Center Washington USA This work was supported by the Semmy Foundation KiKa Children Cancer Free Child Health Research Institute Lucile Packard Foundation for Children’s Health as well as the Stanford CTSA—award number UL1 TR000093—VC Stanford University School of Medicine Dean’s Fellowship VC National Institutes of Neurological Disease and Stroke NINDS grant K08NS070926 Alex’s Lemonade Stand Foundation McKenna Claire Foundation The Cure Starts Now Lyla Nsouli Foundation Connor Johnson Memorial Fund Dylan Jewett Memorial Fund Dylan Frick Memorial Fund Abigail Jensen Memorial Fund Zoey Ganesh Memorial Fund Wayland Villars Memorial Fund and Musella Foundation

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