Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenic in vivo.
Direct experimental evidence shows that tumor growth and metastases are angiogenesis-dependent. Neuroblastoma (NB) is the most common extracranial malignant solid tumor of childhood. In this study, we investigated 2 human NB cell lines, LAN-5 and GI-LI-N, for their capacity to secrete 2 extracellular matrix-degrading enzymes, MMP-2 and MMP-9, and to induce in vitro human microvascular endothelial cells (EC) to proliferate and in vivo angiogenesis in the chick embryo chorio-allantoic membrane (CAM) assay. Conditioned medium (CM) from both cell lines stimulated in vitro EC proliferation and the effect of LAN-5 CM was higher than that of GI-LI-N cells. Moreover, anti-VEGF, but not anti-FGF2 antibodies, prevented growth increment of EC. NB cell lines secreted the active form of MMP-2 almost exclusively, LAN-5 cells more than GI-LI-N cells. Both cell lines, LAN-5 cells more than GI-LI-N ones, induced angiogenesis in the CAM assay. Our data suggest that the 2 NB cell lines are angiogenic, to LAN-5 cells more than GI-LI-N ones. LAN-5 cells are indeed endowed with a more aggressive and invasive phenotype.
Ribatti
D
D
Institute of Human Anatomy, Histology and Embryology, University of Bari Medical School, Italy. ribatti@anatomia.uniba.it
Alessandri
G
G
Vacca
A
A
Iurlaro
M
M
Ponzoni
M
M
D000482:Allantois / Q000098:blood supply; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D017364:Collagenases / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018093:Gelatinases / Q000096:biosynthesis*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D009447:Neuroblastoma / Q000473:pathology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9