title: Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells.
abstract: The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro. Immunohistochemistry demonstrated the expression of angiogenesis markers in both GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel formation. An increased migration aptitude was mainly observed when ECs were cultured in the presence of GCSCs rather than in the presence of PCSCs. These findings suggest that relevant neoangiogenetic events may occur in GBM. In particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the involvement of an autocrine signaling. Moreover, our results suggest that both GCSCs and PCSCs own the skill of activating the "angiogenic switch" and the capability of modulating EC behavior, indicating that both cell types are either responsive to angiogenic stimuli or able to trigger angiogenic response. Together with our previous findings, this study adds a further piece to the challenging puzzle of the characterization of peritumoral tissue and of the definition of its real role in GBM pathophysiology.
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: D'Alessio
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Proietti
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Lama
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Biamonte
authors.affiliation: Institute of Pathology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.affiliation: Institute of Public Health, Hygiene Division,"A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Moscato
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Vescovi
authors.affiliation: Institute of Neurosurgery.
authors.forename: Annunziato
authors.initials: A
authors.lastname: Mangiola
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Angelucci
authors.affiliation: Institute of Histology and Embryology, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gigliola
authors.initials: G
authors.lastname: Sica
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D019898:Autocrine Communication; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D042501:Angiogenic Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C467484:VEGFA protein, human; C501162:FLT1 protein, human; C000588866:KDR protein, human
keywords: angiogenesis; cancer stem cells; glioblastoma; hypoxia; peritumoral tissue