title: Secreted meningeal chemokines, but not VEGFA, modulate the migratory properties of medulloblastoma cells.
abstract: Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the understanding of molecular mechanisms driving this process is nascent. In this study, we examined the secretory chemokine profile of medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned media (CM) of meningothelial cells increased adhesion, spreading and migration of medulloblastoma. VEGFA was identified at elevated levels in the CM from BMEN1 cells (as compared to DAOY CM); however, recombinant VEGFA alone was insufficient to enhance medulloblastoma cell migration. In addition, bevacizumab, the VEGFA scavenging monoclonal antibody, did not block the migratory phenotype induced by the CM. These results reveal that paracrine factors secreted by meningothelial cells can influence migration and adherence of medulloblastoma tumor cells, but VEGFA may not be a specific target for therapeutic intervention in this context.
authors.affiliation: Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: davarem@ohsu.edu.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Davare
authors.affiliation: Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Sangeet
authors.initials: S
authors.lastname: Lal
authors.affiliation: Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Peckham
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Suresh I
authors.initials: SI
authors.lastname: Prajapati
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Sakir H
authors.initials: SH
authors.lastname: Gultekin
authors.affiliation: Department of Anatomic Pathology, Taussig Cancer Center and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; Department Molecular Genetics, Taussig Cancer Center and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195 USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.affiliation: Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: keller@ohsu.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
mesh_terms: D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000276:immunology* / Q000473:pathology; D008578:Meninges / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D018925:Chemokines; D042461:Vascular Endothelial Growth Factor A
keywords: Leptomeningeal metastasis; Medulloblastoma; VEGFA