Production of Platelet-Derived Endothelial Cell Growth Factor by Normal and Transformed Human Cells in Culture

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produc...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1989-10, Vol.86 (19), p.7427-7431
Hauptverfasser: Usuki, Kensuke, Heldin, Nils-Erik, Miyazono, Kohei, Ishikawa, Fuyuki, Takaku, Fumimaro, Westermark, Bengt, Heldin, Carl-Henrik
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container_end_page 7431
container_issue 19
container_start_page 7427
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 86
creator Usuki, Kensuke
Heldin, Nils-Erik
Miyazono, Kohei
Ishikawa, Fuyuki
Takaku, Fumimaro
Westermark, Bengt
Heldin, Carl-Henrik
description Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis.
doi_str_mv 10.1073/pnas.86.19.7427
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We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. 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Aberrant production of PD-ECGF may play a role in tumor angiogenesis.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Antiserum</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>Endothelial cells</subject><subject>Endothelial Growth Factors</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Fibroblasts</subject><subject>Foreskin</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Growth Substances - biosynthesis</subject><subject>Growth Substances - genetics</subject><subject>Growth Substances - pharmacology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Male</subject><subject>Protein hormones. Growth factors. Cytokines</subject><subject>Proteins</subject><subject>Skin - metabolism</subject><subject>Squamous cell carcinoma</subject><subject>Swine</subject><subject>Thyroid cancer</subject><subject>Transcription, Genetic</subject><subject>Tumor cell line</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS1EVUJgjYQE8ga6mtSP8dhesEChD6QKuihr647jIVM542B7Cv33eEhIYQMr2zrfuQ8fhF5QsqBE8tPtAGmhmgXVC1kz-QjNKNG0ampNHqMZIUxWqmb1E_Q0pVtCiBaKHKNj1khFST1Dw3UMq9HmPgw4dPjaQ3be5eqDi_2dW-GzYRXy2vkePF467_FFDN_zGp-DzSHi9h5_CnFTRBhW-CbCkLryLsbLcQPDL0vCfbmMPo_RPUNHHfjknu_POfpyfnazvKyuPl98XL6_qqxgLFdNq8BqIYWuuSRW6kZ0GhxRUirWCgeUKt465kgrqagJaGg54bUVoIBKwefo3a7udmzLNNYNOYI329hvIN6bAL35Wxn6tfka7gzTikhZ_G_3_hi-jS5ls-mTLcvA4MKYjNRMsEb_H6SCy0aWNebodAfaGFKKrjsMQ4mZojRTlEY1hmozRVkcr_7c4cDvsyv6m70OyYLvyufbPj2U1VxQQaY6J3tuavBbfmhkutH77H7kQr7-J1mAlzvgNpX0DwSvG6H5TyLuyVk</recordid><startdate>19891001</startdate><enddate>19891001</enddate><creator>Usuki, Kensuke</creator><creator>Heldin, Nils-Erik</creator><creator>Miyazono, Kohei</creator><creator>Ishikawa, Fuyuki</creator><creator>Takaku, Fumimaro</creator><creator>Westermark, Bengt</creator><creator>Heldin, Carl-Henrik</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19891001</creationdate><title>Production of Platelet-Derived Endothelial Cell Growth Factor by Normal and Transformed Human Cells in Culture</title><author>Usuki, Kensuke ; Heldin, Nils-Erik ; Miyazono, Kohei ; Ishikawa, Fuyuki ; Takaku, Fumimaro ; Westermark, Bengt ; Heldin, Carl-Henrik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-6b8ac957594370c7965f9ae087782b5ea1183be2e0b71540a9ab3034c5a8a1753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Antiserum</topic><topic>Biological and medical sciences</topic><topic>Blood Platelets - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell lines</topic><topic>Cell Transformation, Neoplastic</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>Endothelial cells</topic><topic>Endothelial Growth Factors</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiology</topic><topic>Fibroblasts</topic><topic>Foreskin</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Growth Substances - biosynthesis</topic><topic>Growth Substances - genetics</topic><topic>Growth Substances - pharmacology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Male</topic><topic>Protein hormones. Growth factors. Cytokines</topic><topic>Proteins</topic><topic>Skin - metabolism</topic><topic>Squamous cell carcinoma</topic><topic>Swine</topic><topic>Thyroid cancer</topic><topic>Transcription, Genetic</topic><topic>Tumor cell line</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Usuki, Kensuke</creatorcontrib><creatorcontrib>Heldin, Nils-Erik</creatorcontrib><creatorcontrib>Miyazono, Kohei</creatorcontrib><creatorcontrib>Ishikawa, Fuyuki</creatorcontrib><creatorcontrib>Takaku, Fumimaro</creatorcontrib><creatorcontrib>Westermark, Bengt</creatorcontrib><creatorcontrib>Heldin, Carl-Henrik</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Usuki, Kensuke</au><au>Heldin, Nils-Erik</au><au>Miyazono, Kohei</au><au>Ishikawa, Fuyuki</au><au>Takaku, Fumimaro</au><au>Westermark, Bengt</au><au>Heldin, Carl-Henrik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Production of Platelet-Derived Endothelial Cell Growth Factor by Normal and Transformed Human Cells in Culture</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1989-10-01</date><risdate>1989</risdate><volume>86</volume><issue>19</issue><spage>7427</spage><epage>7431</epage><pages>7427-7431</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>2678104</pmid><doi>10.1073/pnas.86.19.7427</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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ispartof Proceedings of the National Academy of Sciences - PNAS, 1989-10, Vol.86 (19), p.7427-7431
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source Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Analytical, structural and metabolic biochemistry
Animals
Antiserum
Biological and medical sciences
Blood Platelets - metabolism
Cell Division - drug effects
Cell growth
Cell Line
Cell lines
Cell Transformation, Neoplastic
Cells
Cells, Cultured
Endothelial cells
Endothelial Growth Factors
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Fibroblasts
Foreskin
Fundamental and applied biological sciences. Psychology
Gene Expression
Growth Substances - biosynthesis
Growth Substances - genetics
Growth Substances - pharmacology
Humans
Kinetics
Male
Protein hormones. Growth factors. Cytokines
Proteins
Skin - metabolism
Squamous cell carcinoma
Swine
Thyroid cancer
Transcription, Genetic
Tumor cell line
title Production of Platelet-Derived Endothelial Cell Growth Factor by Normal and Transformed Human Cells in Culture
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