title: Novel insights into vascularization patterns and angiogenic factors in glioblastoma subclasses.
abstract: Glioblastoma (GBM) is a highly vascularized and aggressive type of primary brain tumor in adults with dismal survival. Molecular subtypes of GBM have been identified that are related to clinical outcome and response to therapy. Although the mesenchymal type has been ascribed higher angiogenic activity, extensive characterization of the vascular component in GBM subtypes has not been performed. Therefore, we aimed to investigate the differential vascular status and angiogenic signaling levels in molecular subtypes. GBM tissue samples representing proneural IDH1 mutant, classical-like and mesenchymal-like subtypes were analyzed by morphometry for the number of vessels, vessel size and vessel maturity. Also the expression levels of factors from multiple angiogenic signaling pathways were determined. We found that necrotic and hypoxic areas were relatively larger in mesenchymal-like tumors and these tumors also had larger vessels. However, the number of vessels, basement membrane deposition and pericyte coverage did not vary between the subtypes. Regarding signaling patterns the majority of factors were expressed at similar levels in the subtypes, and only ANGPT2, MMP2, TIMP1, VEGFA and MMP9/TIMP2 were higher expressed in GBMs of the classical-like subtype. In conclusion, although morphological differences were observed between the subtypes, the angiogenic signaling status of GBM subtypes seemed to be rather similar. These results challenge the concept of mesenchymal GBMs being more angiogenic than other subclasses.
authors.affiliation: Department of Pathology and Medical Biology (Division of Pathology), University of Groningen, University Medical Center Groningen, HPC EA10, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. s.conroy@umcg.nl.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Conroy
authors.affiliation: Department of Neurosurgery, University of Goningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Wagemakers
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Frank A E
authors.initials: FA
authors.lastname: Kruyt
authors.affiliation: Department of Pathology and Medical Biology (Division of Pathology), University of Groningen, University Medical Center Groningen, HPC EA10, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071231:Carbonic Anhydrase IX / Q000378:metabolism; D015331:Cohort Studies; D000071063:Endoglin / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009336:Necrosis / Q000209:etiology; D009389:Neovascularization, Pathologic / Q000209:etiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; C064206:ENG protein, human; D000071063:Endoglin; D007987:Gonadotropin-Releasing Hormone; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D000071231:Carbonic Anhydrase IX
keywords: Angiogenesis; Glioblastoma; Subclasses; Subtypes