Regulation of Scatter Factor Production via a Soluble Inducing Factor
Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its producti...
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| Veröffentlicht in: | The Journal of cell biology 1994-10, Vol.127 (1), p.225-234 |
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| creator | Rosen, Eliot M. Joseph, Ansamma Jin, Liang Rockwell, Sara Elias, Jack A. Knesel, Jaromir Wines, James McClellan, Jennifer Kluger, M. J. Goldberg, Itzhak D. Zitnik, Ralph |
| description | Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated. We found that various human tumor cell lines that do not produce SF secrete factors that stimulate SF production by fibroblasts, suggesting a paracrine mechanism for regulation of SF production. Conditioned medium from these cell lines contained two distinct scatter factor-inducing factor SF-IF activities: a high molecular weight (>30 kD), heat sensitive activity and a low molecular weight ( |
| doi_str_mv | 10.1083/jcb.127.1.225 |
| format | Article |
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J. ; Goldberg, Itzhak D. ; Zitnik, Ralph</creator><creatorcontrib>Rosen, Eliot M. ; Joseph, Ansamma ; Jin, Liang ; Rockwell, Sara ; Elias, Jack A. ; Knesel, Jaromir ; Wines, James ; McClellan, Jennifer ; Kluger, M. J. ; Goldberg, Itzhak D. ; Zitnik, Ralph</creatorcontrib><description>Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated. We found that various human tumor cell lines that do not produce SF secrete factors that stimulate SF production by fibroblasts, suggesting a paracrine mechanism for regulation of SF production. Conditioned medium from these cell lines contained two distinct scatter factor-inducing factor SF-IF activities: a high molecular weight (>30 kD), heat sensitive activity and a low molecular weight (<30 kD) heat stable activity. Further studies revealed that SF-producing fibroblasts also secrete factors that stimulate their own SF production. We characterized the <30-kD SF-IF activity from ras-3T3 (clone D4), a mouse cell line that overproduces both SF and SF-IF. The <30-kD filtrate from ras-3T3 conditioned medium induced four- to sixfold increases in expression of SF biologic activity, immunoreactive protein, and mRNA by multiple SF-producing fibroblast lines. Ras-3T3 SF-IF activity was stable to boiling, extremes of pH, and reductive alkylation, but was destroyed by proteases. We purified ras-3T3 SF-IF about 10,000-fold from serum-free conditioned medium by a combination of ultrafiltration, cation exchange chromatography, and reverse phase chromatography. The purified protein exhibited electrophoretic mobility of about 12 kD (reduced) and 14 kD (nonreduced) by SDS-PAGE. The identity of the protein was verified by elution of biologic activity from gel slices. Purified SF-IF stimulated SF production in a physiologic concentration range (about 20-400 pM). Its properties and activities were distinct from those of IL-1 and TNF, two known inducers of SF production. We suggest that SF-IF is a physiologic regulator of SF production.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.127.1.225</identifier><identifier>PMID: 7929565</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>3T3 Cells ; Amino acids ; Animals ; Biological Factors - isolation & purification ; Biological Factors - metabolism ; Biological Factors - pharmacology ; Cell growth ; Cell lines ; Cells ; Cellular biology ; Culture Media, Conditioned - chemistry ; Epithelial cells ; Fibroblasts ; Fibroblasts - metabolism ; Gene Expression - drug effects ; Hepatocyte Growth Factor - biosynthesis ; Hepatocyte Growth Factor - genetics ; Hepatocytes ; Humans ; Messenger RNA ; Mice ; Proteins ; RNA, Messenger - biosynthesis ; Stromal cells ; Tumor Cells, Cultured ; Tumors</subject><ispartof>The Journal of cell biology, 1994-10, Vol.127 (1), p.225-234</ispartof><rights>Copyright 1994 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press Oct 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-aa7042673ee485f5aacc77fc8eea37fdf60eac6e725af4f7cef4498c43aab4c33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7929565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rosen, Eliot M.</creatorcontrib><creatorcontrib>Joseph, Ansamma</creatorcontrib><creatorcontrib>Jin, Liang</creatorcontrib><creatorcontrib>Rockwell, Sara</creatorcontrib><creatorcontrib>Elias, Jack A.</creatorcontrib><creatorcontrib>Knesel, Jaromir</creatorcontrib><creatorcontrib>Wines, James</creatorcontrib><creatorcontrib>McClellan, Jennifer</creatorcontrib><creatorcontrib>Kluger, M. J.</creatorcontrib><creatorcontrib>Goldberg, Itzhak D.</creatorcontrib><creatorcontrib>Zitnik, Ralph</creatorcontrib><title>Regulation of Scatter Factor Production via a Soluble Inducing Factor</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated. We found that various human tumor cell lines that do not produce SF secrete factors that stimulate SF production by fibroblasts, suggesting a paracrine mechanism for regulation of SF production. Conditioned medium from these cell lines contained two distinct scatter factor-inducing factor SF-IF activities: a high molecular weight (>30 kD), heat sensitive activity and a low molecular weight (<30 kD) heat stable activity. Further studies revealed that SF-producing fibroblasts also secrete factors that stimulate their own SF production. We characterized the <30-kD SF-IF activity from ras-3T3 (clone D4), a mouse cell line that overproduces both SF and SF-IF. The <30-kD filtrate from ras-3T3 conditioned medium induced four- to sixfold increases in expression of SF biologic activity, immunoreactive protein, and mRNA by multiple SF-producing fibroblast lines. Ras-3T3 SF-IF activity was stable to boiling, extremes of pH, and reductive alkylation, but was destroyed by proteases. We purified ras-3T3 SF-IF about 10,000-fold from serum-free conditioned medium by a combination of ultrafiltration, cation exchange chromatography, and reverse phase chromatography. The purified protein exhibited electrophoretic mobility of about 12 kD (reduced) and 14 kD (nonreduced) by SDS-PAGE. The identity of the protein was verified by elution of biologic activity from gel slices. Purified SF-IF stimulated SF production in a physiologic concentration range (about 20-400 pM). Its properties and activities were distinct from those of IL-1 and TNF, two known inducers of SF production. We suggest that SF-IF is a physiologic regulator of SF production.</description><subject>3T3 Cells</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Biological Factors - isolation & purification</subject><subject>Biological Factors - metabolism</subject><subject>Biological Factors - pharmacology</subject><subject>Cell growth</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Culture Media, Conditioned - chemistry</subject><subject>Epithelial cells</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression - drug effects</subject><subject>Hepatocyte Growth Factor - biosynthesis</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Proteins</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Stromal cells</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtLAzEURoMoWh9LdwqDC3dTk0wymdkIUlotFBQf63Cb3tQp04kmMwX_vdGW-lgF8h2-3JtDyCmjfUaL7Gphpn3GVZ_1OZc7pMekoGnBBN0lPUo5S0vJ5QE5DGFBKRVKZPtkX5W8lLnskeEjzrsa2so1ibPJk4G2RZ-MwLTOJw_ezTrzHa4qSCB5cnU3rTEZN_G-auYb8JjsWagDnmzOI_IyGj4P7tLJ_e14cDNJjeSqTQEUFTxXGaIopJUAxihlTYEImbIzm1MEk6PiEqywyqAVoiyMyACmwmTZEble97510yXODDath1q_-WoJ_kM7qPTfpKle9dytNGecMqViweWmwLv3DkOrl1UwWNfQoOuCZnlBJRNfL138Axeu801cLnYpxiQtygila8h4F4JHu52EUf0lR0c5OsrRTEc5kT__Pf6W3tiI-dk6X4T4qT9lOctlIbJPnMyVdw</recordid><startdate>19941001</startdate><enddate>19941001</enddate><creator>Rosen, Eliot M.</creator><creator>Joseph, Ansamma</creator><creator>Jin, Liang</creator><creator>Rockwell, Sara</creator><creator>Elias, Jack A.</creator><creator>Knesel, Jaromir</creator><creator>Wines, James</creator><creator>McClellan, Jennifer</creator><creator>Kluger, M. J.</creator><creator>Goldberg, Itzhak D.</creator><creator>Zitnik, Ralph</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7TO</scope><scope>5PM</scope></search><sort><creationdate>19941001</creationdate><title>Regulation of Scatter Factor Production via a Soluble Inducing Factor</title><author>Rosen, Eliot M. ; Joseph, Ansamma ; Jin, Liang ; Rockwell, Sara ; Elias, Jack A. ; Knesel, Jaromir ; Wines, James ; McClellan, Jennifer ; Kluger, M. 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J.</creatorcontrib><creatorcontrib>Goldberg, Itzhak D.</creatorcontrib><creatorcontrib>Zitnik, Ralph</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rosen, Eliot M.</au><au>Joseph, Ansamma</au><au>Jin, Liang</au><au>Rockwell, Sara</au><au>Elias, Jack A.</au><au>Knesel, Jaromir</au><au>Wines, James</au><au>McClellan, Jennifer</au><au>Kluger, M. J.</au><au>Goldberg, Itzhak D.</au><au>Zitnik, Ralph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Scatter Factor Production via a Soluble Inducing Factor</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>1994-10-01</date><risdate>1994</risdate><volume>127</volume><issue>1</issue><spage>225</spage><epage>234</epage><pages>225-234</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated. We found that various human tumor cell lines that do not produce SF secrete factors that stimulate SF production by fibroblasts, suggesting a paracrine mechanism for regulation of SF production. Conditioned medium from these cell lines contained two distinct scatter factor-inducing factor SF-IF activities: a high molecular weight (>30 kD), heat sensitive activity and a low molecular weight (<30 kD) heat stable activity. Further studies revealed that SF-producing fibroblasts also secrete factors that stimulate their own SF production. We characterized the <30-kD SF-IF activity from ras-3T3 (clone D4), a mouse cell line that overproduces both SF and SF-IF. The <30-kD filtrate from ras-3T3 conditioned medium induced four- to sixfold increases in expression of SF biologic activity, immunoreactive protein, and mRNA by multiple SF-producing fibroblast lines. Ras-3T3 SF-IF activity was stable to boiling, extremes of pH, and reductive alkylation, but was destroyed by proteases. We purified ras-3T3 SF-IF about 10,000-fold from serum-free conditioned medium by a combination of ultrafiltration, cation exchange chromatography, and reverse phase chromatography. The purified protein exhibited electrophoretic mobility of about 12 kD (reduced) and 14 kD (nonreduced) by SDS-PAGE. The identity of the protein was verified by elution of biologic activity from gel slices. Purified SF-IF stimulated SF production in a physiologic concentration range (about 20-400 pM). Its properties and activities were distinct from those of IL-1 and TNF, two known inducers of SF production. We suggest that SF-IF is a physiologic regulator of SF production.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>7929565</pmid><doi>10.1083/jcb.127.1.225</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of cell biology, 1994-10, Vol.127 (1), p.225-234 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 3T3 Cells Amino acids Animals Biological Factors - isolation & purification Biological Factors - metabolism Biological Factors - pharmacology Cell growth Cell lines Cells Cellular biology Culture Media, Conditioned - chemistry Epithelial cells Fibroblasts Fibroblasts - metabolism Gene Expression - drug effects Hepatocyte Growth Factor - biosynthesis Hepatocyte Growth Factor - genetics Hepatocytes Humans Messenger RNA Mice Proteins RNA, Messenger - biosynthesis Stromal cells Tumor Cells, Cultured Tumors |
| title | Regulation of Scatter Factor Production via a Soluble Inducing Factor |
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