S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis
The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal&qu...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2013, Vol.73 (1), p.172-183 |
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| creator | HIBINO, Toshihiko SAKAGUCHI, Masakiyo MIYAMOTO, Shoko YAMAMOTO, Mami MOTOYAMA, Akira HOSOI, Junichi SHIMOKATA, Tadashi ITO, Tomonobu TSUBOI, Ryoji HUH, Nam-Ho |
| description | The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions. |
| doi_str_mv | 10.1158/0008-5472.CAN-11-3843 |
| format | Article |
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However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-11-3843</identifier><identifier>PMID: 23135911</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Basigin - metabolism ; Biological and medical sciences ; Calgranulin B - metabolism ; Cell Line, Tumor ; Chromatography, Liquid ; Dermatology ; Humans ; Immunohistochemistry ; Immunoprecipitation ; Ligands ; Mass Spectrometry ; Medical sciences ; Melanoma - metabolism ; Mice ; Mice, Transgenic ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Pharmacology. Drug treatments ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Small Interfering ; Tumors ; Tumors of the skin and soft tissue. Premalignant lesions</subject><ispartof>Cancer research (Chicago, Ill.), 2013, Vol.73 (1), p.172-183</ispartof><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-70eb36302bdd3db3579766d932f5490403ea20f14fdbab604241fdbd90bb39963</citedby><cites>FETCH-LOGICAL-c443t-70eb36302bdd3db3579766d932f5490403ea20f14fdbab604241fdbd90bb39963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27062151$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23135911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HIBINO, Toshihiko</creatorcontrib><creatorcontrib>SAKAGUCHI, Masakiyo</creatorcontrib><creatorcontrib>MIYAMOTO, Shoko</creatorcontrib><creatorcontrib>YAMAMOTO, Mami</creatorcontrib><creatorcontrib>MOTOYAMA, Akira</creatorcontrib><creatorcontrib>HOSOI, Junichi</creatorcontrib><creatorcontrib>SHIMOKATA, Tadashi</creatorcontrib><creatorcontrib>ITO, Tomonobu</creatorcontrib><creatorcontrib>TSUBOI, Ryoji</creatorcontrib><creatorcontrib>HUH, Nam-Ho</creatorcontrib><title>S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Basigin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Calgranulin B - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chromatography, Liquid</subject><subject>Dermatology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunoprecipitation</subject><subject>Ligands</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Melanoma - metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neoplasm Invasiveness</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Small Interfering</subject><subject>Tumors</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkFFLwzAQgIMobk5_gpIXwZfOXC5p18cxpg62OXQ-h6RNtdIus-kE_70pmxMCuRzf3eU-Qq6BDQHk6J4xNoqkSPhwMl5GABGOBJ6QPkgcRYkQ8pT0j0yPXHj_GZ4SmDwnPY6AMgXok-krMDZO6cxTTZfu21Z0Xr7rTU5dQaeLxepltqTrD93SVeNq11pPF7bSG1frELTah1P6S3JW6Mrbq8M9IG8P0_XkKZo_P84m43mUCYFtlDBrMEbGTZ5jblAmaRLHeYq8kCJlgqHVnBUgitxoEzPBBYQwT5kxmKYxDsjdvu-2cV8761tVlz6zVfiQdTuvgCfIw4oJBlTu0axx3je2UNumrHXzo4CpzqDq7KjOjgoGQ0p1BkPdzWHEztQ2P1b9KQvA7QHQPtNV0ehNVvp_LmExBwn4C3EXdWg</recordid><startdate>2013</startdate><enddate>2013</enddate><creator>HIBINO, Toshihiko</creator><creator>SAKAGUCHI, Masakiyo</creator><creator>MIYAMOTO, Shoko</creator><creator>YAMAMOTO, Mami</creator><creator>MOTOYAMA, Akira</creator><creator>HOSOI, Junichi</creator><creator>SHIMOKATA, Tadashi</creator><creator>ITO, Tomonobu</creator><creator>TSUBOI, Ryoji</creator><creator>HUH, Nam-Ho</creator><general>American Association for Cancer Research</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>2013</creationdate><title>S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis</title><author>HIBINO, Toshihiko ; SAKAGUCHI, Masakiyo ; MIYAMOTO, Shoko ; YAMAMOTO, Mami ; MOTOYAMA, Akira ; HOSOI, Junichi ; SHIMOKATA, Tadashi ; ITO, Tomonobu ; TSUBOI, Ryoji ; HUH, Nam-Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-70eb36302bdd3db3579766d932f5490403ea20f14fdbab604241fdbd90bb39963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Basigin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Calgranulin B - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chromatography, Liquid</topic><topic>Dermatology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunoprecipitation</topic><topic>Ligands</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Melanoma - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neoplasm Invasiveness</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Small Interfering</topic><topic>Tumors</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HIBINO, Toshihiko</creatorcontrib><creatorcontrib>SAKAGUCHI, Masakiyo</creatorcontrib><creatorcontrib>MIYAMOTO, Shoko</creatorcontrib><creatorcontrib>YAMAMOTO, Mami</creatorcontrib><creatorcontrib>MOTOYAMA, Akira</creatorcontrib><creatorcontrib>HOSOI, Junichi</creatorcontrib><creatorcontrib>SHIMOKATA, Tadashi</creatorcontrib><creatorcontrib>ITO, Tomonobu</creatorcontrib><creatorcontrib>TSUBOI, Ryoji</creatorcontrib><creatorcontrib>HUH, Nam-Ho</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>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HIBINO, Toshihiko</au><au>SAKAGUCHI, Masakiyo</au><au>MIYAMOTO, Shoko</au><au>YAMAMOTO, Mami</au><au>MOTOYAMA, Akira</au><au>HOSOI, Junichi</au><au>SHIMOKATA, Tadashi</au><au>ITO, Tomonobu</au><au>TSUBOI, Ryoji</au><au>HUH, Nam-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2013</date><risdate>2013</risdate><volume>73</volume><issue>1</issue><spage>172</spage><epage>183</epage><pages>172-183</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>23135911</pmid><doi>10.1158/0008-5472.CAN-11-3843</doi><tpages>12</tpages></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antineoplastic agents Basigin - metabolism Biological and medical sciences Calgranulin B - metabolism Cell Line, Tumor Chromatography, Liquid Dermatology Humans Immunohistochemistry Immunoprecipitation Ligands Mass Spectrometry Medical sciences Melanoma - metabolism Mice Mice, Transgenic Neoplasm Invasiveness Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering Tumors Tumors of the skin and soft tissue. Premalignant lesions |
| title | S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis |
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