An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells
EPH receptor A2 (EPHA2) is highly expressed in aggressive types of human cancer, and is expected to be an excellent target molecule for antibody treatments. In this study, we investigated the therapeutic potential of antibody to EPHA2 against melanoma in vitro. We generated three monoclonal antibodi...
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| Veröffentlicht in: | Anticancer research 2018-06, Vol.38 (6), p.3273-3282 |
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| creator | Sakamoto, Atsushi Kato, Kazunori Hasegawa, Toshio Ikeda, Shigaku |
| description | EPH receptor A2 (EPHA2) is highly expressed in aggressive types of human cancer, and is expected to be an excellent target molecule for antibody treatments. In this study, we investigated the therapeutic potential of antibody to EPHA2 against melanoma in vitro.
We generated three monoclonal antibodies (mAbs) to EPHA2 and examined cell-surface expression by flow cytometry. To investigate the ability to inhibit tumor cell migration therapy with mAbs to EPHA2, we performed a wound scratch assay and invasion assay. We investigated the therapeutic effects of immunotoxins consisting of toxin-conjugated EPHA2 mAbs.
All human melanoma cell lines studied expressed EPHA2. Like natural ligand ephrin-A1, one of EPHA2 mAbs, SHM16, inhibited metastatic behavior of cells, such as migration and invasion. In addition, drastic growth inhibition and cytotoxicity were found using immunotoxin-conjugated SHM16.
These observations indicate a promising role for EPHA2 as a target in antibody treatments for melanoma, and demonstrate the potential therapeutic effects of an agonistic antibody to EPHA2. |
| doi_str_mv | 10.21873/anticanres.12592 |
| format | Article |
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We generated three monoclonal antibodies (mAbs) to EPHA2 and examined cell-surface expression by flow cytometry. To investigate the ability to inhibit tumor cell migration therapy with mAbs to EPHA2, we performed a wound scratch assay and invasion assay. We investigated the therapeutic effects of immunotoxins consisting of toxin-conjugated EPHA2 mAbs.
All human melanoma cell lines studied expressed EPHA2. Like natural ligand ephrin-A1, one of EPHA2 mAbs, SHM16, inhibited metastatic behavior of cells, such as migration and invasion. In addition, drastic growth inhibition and cytotoxicity were found using immunotoxin-conjugated SHM16.
These observations indicate a promising role for EPHA2 as a target in antibody treatments for melanoma, and demonstrate the potential therapeutic effects of an agonistic antibody to EPHA2.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>DOI: 10.21873/anticanres.12592</identifier><identifier>PMID: 29848674</identifier><language>eng</language><publisher>Greece: International Institute of Anticancer Research</publisher><subject>Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Anticancer properties ; Antitumor activity ; Cancer ; Cell adhesion & migration ; Cell Line, Tumor ; Cell migration ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cell surface ; Cell Survival - drug effects ; Cytotoxicity ; EphA2 protein ; Flow cytometry ; Growth inhibition ; Humans ; Immunotoxins ; In vitro methods and tests ; Melanoma ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - pathology ; Metastases ; Mice, Inbred BALB C ; Monoclonal antibodies ; Receptor, EphA2 - agonists ; Receptor, EphA2 - immunology ; Receptor, EphA2 - metabolism ; RNA Interference ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Toxicity</subject><ispartof>Anticancer research, 2018-06, Vol.38 (6), p.3273-3282</ispartof><rights>Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</rights><rights>Copyright International Institute of Anticancer Research Jun 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-62546f59d6bef8272fd454fe0e3284e7b61c27f68ecfc58f1b46095fec7d203a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29848674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakamoto, Atsushi</creatorcontrib><creatorcontrib>Kato, Kazunori</creatorcontrib><creatorcontrib>Hasegawa, Toshio</creatorcontrib><creatorcontrib>Ikeda, Shigaku</creatorcontrib><title>An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>EPH receptor A2 (EPHA2) is highly expressed in aggressive types of human cancer, and is expected to be an excellent target molecule for antibody treatments. In this study, we investigated the therapeutic potential of antibody to EPHA2 against melanoma in vitro.
We generated three monoclonal antibodies (mAbs) to EPHA2 and examined cell-surface expression by flow cytometry. To investigate the ability to inhibit tumor cell migration therapy with mAbs to EPHA2, we performed a wound scratch assay and invasion assay. We investigated the therapeutic effects of immunotoxins consisting of toxin-conjugated EPHA2 mAbs.
All human melanoma cell lines studied expressed EPHA2. Like natural ligand ephrin-A1, one of EPHA2 mAbs, SHM16, inhibited metastatic behavior of cells, such as migration and invasion. In addition, drastic growth inhibition and cytotoxicity were found using immunotoxin-conjugated SHM16.
These observations indicate a promising role for EPHA2 as a target in antibody treatments for melanoma, and demonstrate the potential therapeutic effects of an agonistic antibody to EPHA2.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell surface</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>EphA2 protein</subject><subject>Flow cytometry</subject><subject>Growth inhibition</subject><subject>Humans</subject><subject>Immunotoxins</subject><subject>In vitro methods and tests</subject><subject>Melanoma</subject><subject>Melanoma - genetics</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Metastases</subject><subject>Mice, Inbred BALB C</subject><subject>Monoclonal antibodies</subject><subject>Receptor, EphA2 - agonists</subject><subject>Receptor, EphA2 - immunology</subject><subject>Receptor, EphA2 - metabolism</subject><subject>RNA Interference</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Toxicity</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUhoMobk5_gDcS8LozOWk-elnGdMJEBb0uaZtoR5vMpAX37y3b1KsD57zvc-BB6JqSOVAl2Z12fVNpF0ycU-AZnKAplRlNJGfkFE0JcJJIQvgEXcS4IUSITLFzNIFMpUrIdIpec4fzD--aOJJwPvJKX-9w7_HyZZUDXn5_NmXTx_2pHzof8NJaU40b7_Bq6LTDT6bVzncaL0zbxkt0ZnUbzdVxztD7_fJtsUrWzw-Pi3ydVEyoPhHAU2F5VovSWAUSbJ3y1BpiGKjUyFLQCqQVylS24srSMhUk4-NrWQNhms3Q7YG7Df5rMLEvNn4IbnxZAGWSUg4cxhQ9pKrgYwzGFtvQdDrsCkqKvcTiX2Kxlzh2bo7koexM_df4tcZ-ABaRbv0</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Sakamoto, Atsushi</creator><creator>Kato, Kazunori</creator><creator>Hasegawa, Toshio</creator><creator>Ikeda, Shigaku</creator><general>International Institute of Anticancer Research</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>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20180601</creationdate><title>An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells</title><author>Sakamoto, Atsushi ; Kato, Kazunori ; Hasegawa, Toshio ; Ikeda, Shigaku</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-62546f59d6bef8272fd454fe0e3284e7b61c27f68ecfc58f1b46095fec7d203a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell surface</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>EphA2 protein</topic><topic>Flow cytometry</topic><topic>Growth inhibition</topic><topic>Humans</topic><topic>Immunotoxins</topic><topic>In vitro methods and tests</topic><topic>Melanoma</topic><topic>Melanoma - genetics</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - pathology</topic><topic>Metastases</topic><topic>Mice, Inbred BALB C</topic><topic>Monoclonal antibodies</topic><topic>Receptor, EphA2 - agonists</topic><topic>Receptor, EphA2 - immunology</topic><topic>Receptor, EphA2 - metabolism</topic><topic>RNA Interference</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakamoto, Atsushi</creatorcontrib><creatorcontrib>Kato, Kazunori</creatorcontrib><creatorcontrib>Hasegawa, Toshio</creatorcontrib><creatorcontrib>Ikeda, Shigaku</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakamoto, Atsushi</au><au>Kato, Kazunori</au><au>Hasegawa, Toshio</au><au>Ikeda, Shigaku</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>38</volume><issue>6</issue><spage>3273</spage><epage>3282</epage><pages>3273-3282</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>EPH receptor A2 (EPHA2) is highly expressed in aggressive types of human cancer, and is expected to be an excellent target molecule for antibody treatments. In this study, we investigated the therapeutic potential of antibody to EPHA2 against melanoma in vitro.
We generated three monoclonal antibodies (mAbs) to EPHA2 and examined cell-surface expression by flow cytometry. To investigate the ability to inhibit tumor cell migration therapy with mAbs to EPHA2, we performed a wound scratch assay and invasion assay. We investigated the therapeutic effects of immunotoxins consisting of toxin-conjugated EPHA2 mAbs.
All human melanoma cell lines studied expressed EPHA2. Like natural ligand ephrin-A1, one of EPHA2 mAbs, SHM16, inhibited metastatic behavior of cells, such as migration and invasion. In addition, drastic growth inhibition and cytotoxicity were found using immunotoxin-conjugated SHM16.
These observations indicate a promising role for EPHA2 as a target in antibody treatments for melanoma, and demonstrate the potential therapeutic effects of an agonistic antibody to EPHA2.</abstract><cop>Greece</cop><pub>International Institute of Anticancer Research</pub><pmid>29848674</pmid><doi>10.21873/anticanres.12592</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Anticancer properties Antitumor activity Cancer Cell adhesion & migration Cell Line, Tumor Cell migration Cell Movement - drug effects Cell Proliferation - drug effects Cell surface Cell Survival - drug effects Cytotoxicity EphA2 protein Flow cytometry Growth inhibition Humans Immunotoxins In vitro methods and tests Melanoma Melanoma - genetics Melanoma - metabolism Melanoma - pathology Metastases Mice, Inbred BALB C Monoclonal antibodies Receptor, EphA2 - agonists Receptor, EphA2 - immunology Receptor, EphA2 - metabolism RNA Interference Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology Toxicity |
| title | An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells |
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