title: The inhibitor of growth 1 (ING1) proteins suppress angiogenesis and differentially regulate angiopoietin expression in glioblastoma cells.
abstract: The inhibitor of growth 1 (ING1) homologue ING4 has previously been implicated as a negative regulator of angiogenesis in a murine glioma and a multiple myeloma model. An association between ING1 and angiogenesis has not been reported yet. Our previous studies using tumor samples from patients have shown that ING1 levels are downregulated in glioblastoma multiforme (GBM), one of the most highly vascularized malignancies. Based on this background, the goal of this study was to test the effects of the major ING1 splicing isoforms, p47ING1a and p33ING1b, on pathological angiogenesis induced by human GBM cells. We used a chorioallantoic membrane (CAM) assay to examine whether LN229 human GBM cells can induce angiogenesis and whether alterations in ING1 expression, such as ING1 knockdown by siRNA or ectopic ING1 overexpression using ING1a and ING1b expression constructs, can affect this process. Increased ING1 protein expression significantly suppressed LN229 cell-induced angiogenesis in the CAM assay. While no effects on the proangiogenic factors VEGF or IL-8 were noted, the expression of angiopoietins (Ang) 1 and 4 were increased by the p47ING1a, but not by the p33ING1b isoform. Levels of Ang-2 were not sensitive to altered ING1 levels. Our data are the first to suggest that ING1 proteins suppress neoangiogenesis in GBM. Moreover, our results may support the idea that ING1 proteins regulate the expression of proteins that are critical for angiogenesis in GBM such as the angiopoietins.
authors.affiliation: Department of Pediatric Oncology/Haematology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany. gesche.tallen@charite.de
authors.forename: Gesche
authors.initials: G
authors.lastname: Tallen
authors.forename: Sonja
authors.initials: S
authors.lastname: Farhangi
authors.forename: Mona
authors.initials: M
authors.lastname: Tamannai
authors.forename: Nikola
authors.initials: N
authors.lastname: Holtkamp
authors.forename: Dorothea
authors.initials: D
authors.lastname: Mangoldt
authors.forename: Sitar
authors.initials: S
authors.lastname: Shah
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Matthias
authors.initials: M
authors.lastname: Truss
authors.forename: Guenter
authors.initials: G
authors.lastname: Henze
authors.forename: Karl
authors.initials: K
authors.lastname: Riabowol
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D042682:Angiopoietins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A