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 |
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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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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.</description><identifier>ISSN: 0002-9629</identifier><identifier>EISSN: 1538-2990</identifier><identifier>DOI: 10.1097/00000441-199007000-00003</identifier><identifier>PMID: 2196796</identifier><identifier>CODEN: AJMSA9</identifier><language>eng</language><publisher>Hagerstown, MD: Elsevier Inc</publisher><subject>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</subject><ispartof>The American journal of the medical sciences, 1990-07, Vol.300 (1), p.9-15</ispartof><rights>1990 Southern Society for Clinical Investigation</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-91ce6685a0ba40f57d13deee9ead1e80f0d3158fc36fe803cb145970783331aa3</citedby><cites>FETCH-LOGICAL-c398t-91ce6685a0ba40f57d13deee9ead1e80f0d3158fc36fe803cb145970783331aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4425819$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2196796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Stefano, John F.</creatorcontrib><creatorcontrib>Kirchner, Michele</creatorcontrib><creatorcontrib>Dagenhardt, Kurt</creatorcontrib><creatorcontrib>Hagag, Nabil</creatorcontrib><title>Activation of Cancer Cell Proteases and Cytotoxicity by EGF and PDGF Growth Factors</title><title>The American journal of the medical sciences</title><addtitle>Am J Med Sci</addtitle><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.</description><subject>Amiloride - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cycloheximide - pharmacology</subject><subject>Enzyme Activation</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Growth Factor</subject><subject>Hemolysis - drug effects</subject><subject>Humans</subject><subject>Leupeptins - pharmacology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Peptide Hydrolases - metabolism</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Proteases</subject><subject>Tosyllysine Chloromethyl Ketone - pharmacology</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Tumor Cells, Cultured - enzymology</subject><subject>Tumors</subject><issn>0002-9629</issn><issn>1538-2990</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PAyEQhonRaP34CSYcjLdVZtld4KirrSYmmqhnQtnZiGmLAq3230tt7dW5MPPOO8PkIYQCuwCmxCVbRVVBAUoxJnJRrBS-QwZQc1mUWd4lgyyVhWpKdUAOY3xnDEoJfJ_sl6AaoZoBeb6yyS1Mcn5GfU9bM7MYaIuTCX0KPqGJGKmZdbRdJp_8t7MuLel4SW9Hw1_96SYno-C_0hsdGpt8iMdkrzeTiCeb94i8Dm9f2rvi4XF03149FJYrmQoFFptG1oaNTcX6WnTAO0RUaDpAyXrWcahlb3nT55LbMVS1EkxIzjkYw4_I-XrvR_Cfc4xJT120-XQzQz-PWigpRQ0iG-XaaIOPMWCvP4KbmrDUwPSKp_7jqbc8fyWeR083f8zHU-y2gxuAuX-26ZtozaQPGaCLW1tVlbUElW3XaxtmHguHQUfrMLPuXECbdOfd_7f8AKxHj-I</recordid><startdate>19900701</startdate><enddate>19900701</enddate><creator>Di Stefano, John F.</creator><creator>Kirchner, Michele</creator><creator>Dagenhardt, Kurt</creator><creator>Hagag, Nabil</creator><general>Elsevier Inc</general><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19900701</creationdate><title>Activation of Cancer Cell Proteases and Cytotoxicity by EGF and PDGF Growth Factors</title><author>Di Stefano, John F. ; Kirchner, Michele ; Dagenhardt, Kurt ; Hagag, Nabil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-91ce6685a0ba40f57d13deee9ead1e80f0d3158fc36fe803cb145970783331aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Amiloride - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Cycloheximide - pharmacology</topic><topic>Enzyme Activation</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Growth Factor</topic><topic>Hemolysis - drug effects</topic><topic>Humans</topic><topic>Leupeptins - pharmacology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Peptide Hydrolases - metabolism</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Proteases</topic><topic>Tosyllysine Chloromethyl Ketone - pharmacology</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - enzymology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Stefano, John F.</creatorcontrib><creatorcontrib>Kirchner, Michele</creatorcontrib><creatorcontrib>Dagenhardt, Kurt</creatorcontrib><creatorcontrib>Hagag, Nabil</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of the medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Stefano, John F.</au><au>Kirchner, Michele</au><au>Dagenhardt, Kurt</au><au>Hagag, Nabil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of Cancer Cell Proteases and Cytotoxicity by EGF and PDGF Growth Factors</atitle><jtitle>The American journal of the medical sciences</jtitle><addtitle>Am J Med Sci</addtitle><date>1990-07-01</date><risdate>1990</risdate><volume>300</volume><issue>1</issue><spage>9</spage><epage>15</epage><pages>9-15</pages><issn>0002-9629</issn><eissn>1538-2990</eissn><coden>AJMSA9</coden><abstract>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.</abstract><cop>Hagerstown, MD</cop><pub>Elsevier Inc</pub><pmid>2196796</pmid><doi>10.1097/00000441-199007000-00003</doi><tpages>7</tpages></addata></record> |
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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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