Aminopeptidase A is a functional target in angiogenic blood vessels
We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected...
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| Veröffentlicht in: | Cancer cell 2004-02, Vol.5 (2), p.151-162 |
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| creator | Marchiò, Serena Lahdenranta, Johanna Schlingemann, Reinier O Valdembri, Donatella Wesseling, Pieter Arap, Marco A Hajitou, Amin Ozawa, Michael G Trepel, Martin Giordano, Ricardo J Nanus, David M Dijkman, Henri B.P.M Oosterwijk, Egbert Sidman, Richard L Cooper, Max D Bussolino, Federico Pasqualini, Renata Arap, Wadih |
| description | We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target. |
| doi_str_mv | 10.1016/S1535-6108(04)00025-X |
| format | Article |
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To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/S1535-6108(04)00025-X</identifier><identifier>PMID: 14998491</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Motifs ; Animals ; Blood Vessels ; Cell Division ; Cell Hypoxia - physiology ; Cell Movement ; Chick Embryo ; Endothelial Cells - physiology ; Enzyme Inhibitors ; Glutamyl Aminopeptidase - metabolism ; Growth Substances - metabolism ; Humans ; Mice ; Mice, Knockout ; Microscopy, Fluorescence ; Neoplasms - metabolism ; Neovascularization, Pathologic ; Peptide Library ; Peptides - metabolism ; Protein Binding ; Transplantation, Heterologous - pathology</subject><ispartof>Cancer cell, 2004-02, Vol.5 (2), p.151-162</ispartof><rights>2004 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-74b1f228861453e325d3868af5aafbc888f9e70b8fc76b6d33b8431bbcafd0d63</citedby><cites>FETCH-LOGICAL-c410t-74b1f228861453e325d3868af5aafbc888f9e70b8fc76b6d33b8431bbcafd0d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S153561080400025X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14998491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marchiò, Serena</creatorcontrib><creatorcontrib>Lahdenranta, Johanna</creatorcontrib><creatorcontrib>Schlingemann, Reinier O</creatorcontrib><creatorcontrib>Valdembri, Donatella</creatorcontrib><creatorcontrib>Wesseling, Pieter</creatorcontrib><creatorcontrib>Arap, Marco A</creatorcontrib><creatorcontrib>Hajitou, Amin</creatorcontrib><creatorcontrib>Ozawa, Michael G</creatorcontrib><creatorcontrib>Trepel, Martin</creatorcontrib><creatorcontrib>Giordano, Ricardo J</creatorcontrib><creatorcontrib>Nanus, David M</creatorcontrib><creatorcontrib>Dijkman, Henri B.P.M</creatorcontrib><creatorcontrib>Oosterwijk, Egbert</creatorcontrib><creatorcontrib>Sidman, Richard L</creatorcontrib><creatorcontrib>Cooper, Max D</creatorcontrib><creatorcontrib>Bussolino, Federico</creatorcontrib><creatorcontrib>Pasqualini, Renata</creatorcontrib><creatorcontrib>Arap, Wadih</creatorcontrib><title>Aminopeptidase A is a functional target in angiogenic blood vessels</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. 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These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.</description><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Blood Vessels</subject><subject>Cell Division</subject><subject>Cell Hypoxia - physiology</subject><subject>Cell Movement</subject><subject>Chick Embryo</subject><subject>Endothelial Cells - physiology</subject><subject>Enzyme Inhibitors</subject><subject>Glutamyl Aminopeptidase - metabolism</subject><subject>Growth Substances - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microscopy, Fluorescence</subject><subject>Neoplasms - metabolism</subject><subject>Neovascularization, Pathologic</subject><subject>Peptide Library</subject><subject>Peptides - metabolism</subject><subject>Protein Binding</subject><subject>Transplantation, Heterologous - pathology</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKxDAUhoMojo4-gpKV6KKaNG2armQYvMGACxVmF3I5GSJtU5t2wLe3cxGXrs5ZfP_5OR9CF5TcUkL53RvNWZ5wSsQ1yW4IIWmeLA_QCRWFSBgX_HDcf5EJOo3xk4w5WpTHaEKzshRZSU_QfFb7JrTQ9t6qCHiGfcQKu6ExvQ-NqnCvuhX02DdYNSsfVtB4g3UVgsVriBGqeIaOnKoinO_nFH08PrzPn5PF69PLfLZITEZJnxSZpi5NheA0yxmwNLdMcKFcrpTTRgjhSiiIFs4UXHPLmBYZo1ob5SyxnE3R1e5u24WvAWIvax8NVJVqIAxRFrQgjJN0BPMdaLoQYwdOtp2vVfctKZEbe3JrT27USJLJrT25HHOX-4JB12D_UntdI3C_A8avYe2hk9F4aAxY34HppQ3-n4ofIUl_LQ</recordid><startdate>20040201</startdate><enddate>20040201</enddate><creator>Marchiò, Serena</creator><creator>Lahdenranta, Johanna</creator><creator>Schlingemann, Reinier O</creator><creator>Valdembri, Donatella</creator><creator>Wesseling, Pieter</creator><creator>Arap, Marco A</creator><creator>Hajitou, Amin</creator><creator>Ozawa, Michael G</creator><creator>Trepel, Martin</creator><creator>Giordano, Ricardo J</creator><creator>Nanus, David M</creator><creator>Dijkman, Henri B.P.M</creator><creator>Oosterwijk, Egbert</creator><creator>Sidman, Richard L</creator><creator>Cooper, Max D</creator><creator>Bussolino, Federico</creator><creator>Pasqualini, Renata</creator><creator>Arap, Wadih</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>20040201</creationdate><title>Aminopeptidase A is a functional target in angiogenic blood vessels</title><author>Marchiò, Serena ; Lahdenranta, Johanna ; Schlingemann, Reinier O ; Valdembri, Donatella ; Wesseling, Pieter ; Arap, Marco A ; Hajitou, Amin ; Ozawa, Michael G ; Trepel, Martin ; Giordano, Ricardo J ; Nanus, David M ; Dijkman, Henri B.P.M ; Oosterwijk, Egbert ; Sidman, Richard L ; Cooper, Max D ; Bussolino, Federico ; Pasqualini, Renata ; Arap, Wadih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-74b1f228861453e325d3868af5aafbc888f9e70b8fc76b6d33b8431bbcafd0d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Motifs</topic><topic>Animals</topic><topic>Blood Vessels</topic><topic>Cell Division</topic><topic>Cell Hypoxia - physiology</topic><topic>Cell Movement</topic><topic>Chick Embryo</topic><topic>Endothelial Cells - physiology</topic><topic>Enzyme Inhibitors</topic><topic>Glutamyl Aminopeptidase - metabolism</topic><topic>Growth Substances - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microscopy, Fluorescence</topic><topic>Neoplasms - metabolism</topic><topic>Neovascularization, Pathologic</topic><topic>Peptide Library</topic><topic>Peptides - metabolism</topic><topic>Protein Binding</topic><topic>Transplantation, Heterologous - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marchiò, Serena</creatorcontrib><creatorcontrib>Lahdenranta, Johanna</creatorcontrib><creatorcontrib>Schlingemann, Reinier O</creatorcontrib><creatorcontrib>Valdembri, Donatella</creatorcontrib><creatorcontrib>Wesseling, Pieter</creatorcontrib><creatorcontrib>Arap, Marco A</creatorcontrib><creatorcontrib>Hajitou, Amin</creatorcontrib><creatorcontrib>Ozawa, Michael G</creatorcontrib><creatorcontrib>Trepel, Martin</creatorcontrib><creatorcontrib>Giordano, Ricardo J</creatorcontrib><creatorcontrib>Nanus, David M</creatorcontrib><creatorcontrib>Dijkman, Henri B.P.M</creatorcontrib><creatorcontrib>Oosterwijk, Egbert</creatorcontrib><creatorcontrib>Sidman, Richard L</creatorcontrib><creatorcontrib>Cooper, Max D</creatorcontrib><creatorcontrib>Bussolino, Federico</creatorcontrib><creatorcontrib>Pasqualini, Renata</creatorcontrib><creatorcontrib>Arap, Wadih</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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 cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marchiò, Serena</au><au>Lahdenranta, Johanna</au><au>Schlingemann, Reinier O</au><au>Valdembri, Donatella</au><au>Wesseling, Pieter</au><au>Arap, Marco A</au><au>Hajitou, Amin</au><au>Ozawa, Michael G</au><au>Trepel, Martin</au><au>Giordano, Ricardo J</au><au>Nanus, David M</au><au>Dijkman, Henri B.P.M</au><au>Oosterwijk, Egbert</au><au>Sidman, Richard L</au><au>Cooper, Max D</au><au>Bussolino, Federico</au><au>Pasqualini, Renata</au><au>Arap, Wadih</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aminopeptidase A is a functional target in angiogenic blood vessels</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>5</volume><issue>2</issue><spage>151</spage><epage>162</epage><pages>151-162</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. 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| ispartof | Cancer cell, 2004-02, Vol.5 (2), p.151-162 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Motifs Animals Blood Vessels Cell Division Cell Hypoxia - physiology Cell Movement Chick Embryo Endothelial Cells - physiology Enzyme Inhibitors Glutamyl Aminopeptidase - metabolism Growth Substances - metabolism Humans Mice Mice, Knockout Microscopy, Fluorescence Neoplasms - metabolism Neovascularization, Pathologic Peptide Library Peptides - metabolism Protein Binding Transplantation, Heterologous - pathology |
| title | Aminopeptidase A is a functional target in angiogenic blood vessels |
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