Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasminogen activator liberated by cells of human neuroblastoma strain SK-N-SH was purified up to 400-fold, with a 40% recovery of activity, by a relatively simple procedure. This involved (NH4)2SO4 precipitation, followed by chromatography on both Affi-Gel Blue and p-aminobenzaminidine-Sepharose. The SK-N-SH activator was shown to differ from human urokinase with respect to immunological specificity, the molecular weights and isoelectric points of their enzymatically active species, the ability to be activated by fibrin and their relative sensitivities to inactivation by diisopropyl fluorophosphate. The average molecular weights of the enzymatically active species derived from strain SK-N-SH were shown to be 66,500, 64,500, 60,500 and 37,500. In the presence of fibrin, the SK-N-SH plasminogen activator appeared to be stimulated approximately 16-fold, with no apparent stimulation of urokinase activity. Urokinase is inactivated by diisopropyl fluorophosphate at a rate 6.4-fold faster than that of the SK-N-SH activator.
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PMID:Characterization and partial purification of the plasminogen activator from human neuroblastoma cell line, SK-N-SH. A comparison with human urokinase. 705 33

Proteases of the plasminogen-plasminogen activator (PA) system play an important role in cancer metastasis. We have examined the expression of these proteases and their cell surface receptors and inhibitors in neuroblastoma, a tumor that originates in cells of the neural crest and is the second most common solid tumor in children. This analysis was performed in seven established human cell lines and 20 primary tumor specimens. Urokinase PA and, in particular, tissue-type PA were expressed in cell lines and in tumor tissues; however, their levels of expression did not correlate with clinical stage. There was little evidence suggesting that neuroblastoma cells concentrate PA activity at their cell surface because urokinase-type PA receptor mRNA was detected in two cell lines and in 5 of 20 tumor samples by reverse transcription-PCR only. PA inhibitor (PAI)-2 was absent in all cell lines and tumor tissue samples examined. However, PAI-1, which was not expressed by the cell lines, was expressed by stromal cells and, specifically, endothelial cells in tumor tissue. By extending the analysis of PAI-1 expression in 64 primary tumor specimens, we found that high PAI-1 expression paradoxically correlated with metastatic stage and tumor recurrence. In vitro experiments indicated that the expression of PAI-1 by human microvascular endothelial cells was stimulated in the presence of SK-N-BE(2) human neuroblastoma cells and neuroblastoma culture medium. Recombinant PAI-1 also promoted SK-N-BE(2) cell detachment from vitronectin and migration from vitronectin toward fibronectin. From these data, we conclude that the up-regulation of PAI-1 expression in endothelial cells may promote rather than inhibit metastasis in neuroblastoma.
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PMID:The plasminogen-plasminogen activator (PA) system in neuroblastoma: role of PA inhibitor-1 in metastasis. 1009 67