title: Podoplanin: a marker for reactive gliosis in gliomas and brain injury.
abstract: Reactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic protein-positive astrocytes within and adjacent to gliomas. The expression of PDPN in tumor-associated reactive astrocytes was confirmed by its colocalization with the astrocytic marker S100β and with connexin43, a major astrocytic gap junction protein. To determine whether the increase in PDPN is a general feature of gliosis, we used 2 mouse models in which astrogliosis was induced either by a needle injury or ischemia and observed similar upregulation of PDPN in reactive astrocytes in both models. Astrocytic PDPN was also found to be coexpressed with nestin, an intermediate filament marker for neural stem/progenitor cells. Our findings confirm that expression of PDPN is part of the normal host response to brain injury and gliomas, and suggest that it may be a novel cell surface marker for a specific population of reactive astrocytes in the vicinity of gliomas and nonneoplastic brain lesions. The findings also highlight the heterogeneity of glial fibrillary acidic protein-positive astrocytes in reactive gliosis.
authors.affiliation: From the Department of Cellular and Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada (KK, MF-A, JFB, CCN, WCS); and Department of Molecular Biology and Graduate School of Biomedical Sciences, Rowan University School of Medicine, Stratford, New Jersey (HK, GSG).
authors.forename: Kushal
authors.initials: K
authors.lastname: Kolar
authors.forename: Moises
authors.initials: M
authors.lastname: Freitas-Andrade
authors.forename: John F
authors.initials: JF
authors.lastname: Bechberger
authors.forename: Harini
authors.initials: H
authors.lastname: Krishnan
authors.forename: Gary S
authors.initials: GS
authors.lastname: Goldberg
authors.forename: Christian C
authors.initials: CC
authors.lastname: Naus
authors.forename: Wun Chey
authors.initials: WC
authors.lastname: Sin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000473:pathology*; D005911:Gliosis / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D002135:Calcium-Binding Proteins; D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D064231:Nestin; D064568:S100 Calcium Binding Protein beta Subunit; C491049:Aif1 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin