Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenicin vivo

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Abstract
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. Int. J. Cancer 77:449–454, 1998.