Activation of Cancer Cell Proteases and Cytotoxicity by EGF and PDGF Growth Factors

The biological effects of EGF and PDGF growth factors on A172 and hEGFr-3T3 cell lines were studied using RBC induced cytolysis and polyacrylamide-gelatin gel electrophoresis assays. The authors report that growth factor-induced cytotoxicity in these cells is mediated by proteolytic enzymes. Treatme...

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Veröffentlicht in:The American journal of the medical sciences 1990-07, Vol.300 (1), p.9-15
Hauptverfasser: Di Stefano, John F., Kirchner, Michele, Dagenhardt, Kurt, Hagag, Nabil
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container_title The American journal of the medical sciences
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creator Di Stefano, John F.
Kirchner, Michele
Dagenhardt, Kurt
Hagag, Nabil
description The biological effects of EGF and PDGF growth factors on A172 and hEGFr-3T3 cell lines were studied using RBC induced cytolysis and polyacrylamide-gelatin gel electrophoresis assays. The authors report that growth factor-induced cytotoxicity in these cells is mediated by proteolytic enzymes. Treatment of A172 cells with either EGF or PDGF resulted in marked increase of their cytotoxicity (Release Index = 150%). Similarly, RBC induced release index by hEGFr-3T3 cells was elevated to 420% in the presence of 3.4 pM of EGF. However, in A172 cells, PDGF did not have a significant effect on DNA and protein synthesis indicating that stimulation of proteolytic activity is independent of the growth factor signaling pathway. Growth factor induced cytotoxicity was significantly reduced by protease inhibitors in both cell lines. Using EDTA and leupeptin several proteolytic species were identified and localized to cellular membranes as evidenced by polyacrylamide-gelatin electrophoresis assay. These data suggest that growth factors regulate the activation or secretion of proteolytic enzymes in cancer cells and may mediate the invasive and metastatic behavior of these cells.
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source MEDLINE; Journals@Ovid Complete; Alma/SFX Local Collection
subjects Amiloride - pharmacology
Animals
Biological and medical sciences
Cancer
Cell Line
Cell Survival - drug effects
Cells, Cultured
Cycloheximide - pharmacology
Enzyme Activation
Epidermal Growth Factor - pharmacology
Growth Factor
Hemolysis - drug effects
Humans
Leupeptins - pharmacology
Medical sciences
Mice
Peptide Hydrolases - metabolism
Platelet-Derived Growth Factor - pharmacology
Proteases
Tosyllysine Chloromethyl Ketone - pharmacology
Tumor Cells, Cultured - drug effects
Tumor Cells, Cultured - enzymology
Tumors
title Activation of Cancer Cell Proteases and Cytotoxicity by EGF and PDGF Growth Factors
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