title: A proteome comparison between physiological angiogenesis and angiogenesis in glioblastoma.
abstract: The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made. The approach yielded 29 and 12 differentially expressed proteins for glioblastoma and endometrium blood vessels, respectively. The aberrant expression of five proteins, i.e. periostin, tenascin-C, TGF-beta induced protein, integrin alpha-V, and laminin subunit beta-2 were validated by immunohistochemistry. In addition, pathway analysis of the differentially expressed proteins was performed and significant differences in the usage of angiogenic pathways were found. We conclude that there are essential differences in protein expression profiles between tumor and normal physiological angiogenesis.
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Dana A M
authors.initials: DA
authors.lastname: Mustafa
authors.forename: Lennard J
authors.initials: LJ
authors.lastname: Dekker
authors.forename: Christoph
authors.initials: C
authors.lastname: Stingl
authors.forename: Andreas
authors.initials: A
authors.lastname: Kremer
authors.forename: Marcel
authors.initials: M
authors.lastname: Stoop
authors.forename: Peter A E
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply*; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D020543:Proteome / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D039564:Integrin alphaV; D007797:Laminin; C512835:POSTN protein, human; D020543:Proteome; D019063:Tenascin; D016212:Transforming Growth Factor beta