title: CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells.
abstract: CXCL12 (stromal cell-derived factor-1/CXCL12) regulates leukocyte, endothelial and hematopoietic precursor migration, bone-marrow myelopoiesis and angiogenesis. CXCL12 and its receptor CXCR4 are over-expressed in malignant gliomas, which are highly vascularized tumors with a poor prognosis. We studied the expression of CXCL12 and CXCR4 in glioma cell lines, endothelial cells, tissue sections and endocavitary fluids from patients with gliomas. We then analyzed the proliferative and the apoptotic effect of CXCL12 in endothelial cells and glioma primary cultures. We observed the release of CXCL12 in supernatants of human brain microvascular endothelial cells and at variable levels, in post-surgical endocavitary fluids. CXCL12 was expressed in both glioma and endothelial cells as assessed by immunostaining of surgical brain sections. CXCR4 was found in cells lines and primary cultures from malignant gliomas as well as in endothelial cells and was increased by vascular endothelial growth factor and basic fibroblast growth factor (bFGF). CXCL12 inhibited bFGF-induced proliferation of endothelial cells and increased the survival of endothelial cells. The survival of primary cells obtained from glioma specimens was also enhanced in the presence of CXCL12. We point out the presence and the release of CXCL12 in tumor microenvironment and we observed a modulating effect of CXCL12 on proliferation and survival of both endothelial and tumoral cells. Our data support in vivo studies suggesting a role in angiogenesis played by CXCL12, which could represent a possible prognostic factor.
authors.affiliation: Istituto Nazionale Neurologico Carlo Besta, Milan, Italy. laboratorio_analisi@istituto-besta.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Salmaggi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gelati
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
authors.forename: Simona
authors.initials: S
authors.lastname: Frigerio
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Silvani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Broggi
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Danilo
authors.initials: D
authors.lastname: Croci
authors.forename: Amerigo
authors.initials: A
authors.lastname: Boiardi
authors.forename: Marco
authors.initials: M
authors.lastname: De Rossi
mesh_terms: D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005910:Glioma / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2