title: PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells.
abstract: Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brooks
authors.affiliation: BRIGHT Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America; Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: Jackson
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Forys
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Leonard
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kim
authors.affiliation: BRIGHT Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America; Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.affiliation: Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Robi D
authors.initials: RD
authors.lastname: Mitra
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Rubin
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D055153:Stem Cell Niche / Q000502:physiology
chemical_list: D054708:Cyclic Nucleotide Phosphodiesterases, Type 7