Modulation of proteolytic potential and differentiation by CNTF and BDNF in two mouse neuroblastoma clones: relation to invasion.
The effect of CNTF and BDNF on a proteolytic complement instrumental to invasion and on differentiation was studied in two murine neuroblastoma clones, N1 and N7. At the membrane level, gelatinase MMP-2--mainly the activated form--was restrained by CNTF and BDNF to a residual 34% with both factors; membrane-type 1 MMP was down-regulated to 50% (10 h) and 34% (24 h) with both factors; and urokinase-type plasminogen activator was restrained mainly by BDNF to 70%. In the medium, the two gelatinases MMP-2 and MMP-9 were mainly in zymogen form: only MMP-2 was restrained in N1 cells, while only MMP-9 was restrained in N7 cells by both factors, single or in combination. These effects were paralleled by the induction of neurite outgrowth, which was more stimulated in the less differentiated clone. These dose-dependent and transient effects make CNTF and BDNF ideal candidates for constraining the potentially invasive behavior of nervous system tumors.
Sartor
Luigi
L
Department of Experimental Biomedical Sciences, Medical School of Padova, Padova, Italy.
Negro
Alessandro
A
Barletta
Emanuela
E
Mugnai
Gabriele
G
Garbisa
Spiridione
S
D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D002999:Clone Cells; D017931:DNA Primers; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D017931:DNA Primers; D010450:Endopeptidases; D020782:Matrix Metalloproteinases