Reduced expression of hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) in human glioblastomas: Implication for anti‐invasive role of HAI‐2/PB in glioblastoma cells
Hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) is a serine proteinase inhibitor that contains 2 Kunitz‐domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to he...
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| Veröffentlicht in: | International journal of cancer 2001-08, Vol.93 (3), p.339-345 |
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| container_title | International journal of cancer |
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| creator | Hamasuna, Ryouichi Kataoka, Hiroaki Meng, Jing‐Yan Itoh, Hiroshi Moriyama, Takuzou Wakisaka, Shinichiro Koono, Masashi |
| description | Hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) is a serine proteinase inhibitor that contains 2 Kunitz‐domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI‐2/PB in human gliomas in vivo and the effects of HAI‐2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI‐2/PB mRNA was expressed in normal brain and in low‐grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI‐2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG‐1) were transiently transfected with an expression vector harboring human HAI‐2/PB cDNA. Subsequent analysis indicated that the expression of HAI‐2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI‐2/PB inhibited Matrigel invasion of U251 and YKG‐1 cells by 30% and 64%, respectively. This anti‐invasive effect appeared to be mediated primarily by the inhibitory activity of HAI‐2/PB against the serine proteinase‐dependent matrix degradation. These findings suggest that the reduced expression of HAI‐2/PB is possibly involved in the progression of human gliomas. © 2001 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/ijc.1349 |
| format | Article |
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It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI‐2/PB in human gliomas in vivo and the effects of HAI‐2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI‐2/PB mRNA was expressed in normal brain and in low‐grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI‐2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG‐1) were transiently transfected with an expression vector harboring human HAI‐2/PB cDNA. Subsequent analysis indicated that the expression of HAI‐2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI‐2/PB inhibited Matrigel invasion of U251 and YKG‐1 cells by 30% and 64%, respectively. This anti‐invasive effect appeared to be mediated primarily by the inhibitory activity of HAI‐2/PB against the serine proteinase‐dependent matrix degradation. These findings suggest that the reduced expression of HAI‐2/PB is possibly involved in the progression of human gliomas. © 2001 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.1349</identifier><identifier>PMID: 11433397</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Astrocytoma - genetics ; Astrocytoma - metabolism ; Biological and medical sciences ; Blotting, Northern ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Collagen - chemistry ; DNA Primers - chemistry ; Drug Combinations ; Fibrin - metabolism ; glioblastoma ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Hepatocyte Growth Factor - metabolism ; HGF ; HGF activator inhibitor type‐2 ; Humans ; Immunoblotting ; invasion ; Laminin - chemistry ; Medical sciences ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Neoplasm Invasiveness ; Neurology ; Proteoglycans - chemistry ; Proto-Oncogene Proteins c-met - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - metabolism ; RNA, Messenger - metabolism ; Serine Endopeptidases - metabolism ; Serine Proteinase Inhibitors - genetics ; Serine Proteinase Inhibitors - metabolism ; Transfection ; Trypsin Inhibitor, Kunitz Soybean ; Tumors of the nervous system. Phacomatoses</subject><ispartof>International journal of cancer, 2001-08, Vol.93 (3), p.339-345</ispartof><rights>Copyright © 2001 Wiley‐Liss, Inc.</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2001 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3289-db015e87b39655fc6a868b5003ce65aca410312c69771279d88eb276b8d78a1a3</citedby><cites>FETCH-LOGICAL-c3289-db015e87b39655fc6a868b5003ce65aca410312c69771279d88eb276b8d78a1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.1349$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.1349$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14080419$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11433397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hamasuna, Ryouichi</creatorcontrib><creatorcontrib>Kataoka, Hiroaki</creatorcontrib><creatorcontrib>Meng, Jing‐Yan</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><creatorcontrib>Moriyama, Takuzou</creatorcontrib><creatorcontrib>Wakisaka, Shinichiro</creatorcontrib><creatorcontrib>Koono, Masashi</creatorcontrib><title>Reduced expression of hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) in human glioblastomas: Implication for anti‐invasive role of HAI‐2/PB in glioblastoma cells</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) is a serine proteinase inhibitor that contains 2 Kunitz‐domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI‐2/PB in human gliomas in vivo and the effects of HAI‐2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI‐2/PB mRNA was expressed in normal brain and in low‐grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI‐2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG‐1) were transiently transfected with an expression vector harboring human HAI‐2/PB cDNA. Subsequent analysis indicated that the expression of HAI‐2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI‐2/PB inhibited Matrigel invasion of U251 and YKG‐1 cells by 30% and 64%, respectively. This anti‐invasive effect appeared to be mediated primarily by the inhibitory activity of HAI‐2/PB against the serine proteinase‐dependent matrix degradation. These findings suggest that the reduced expression of HAI‐2/PB is possibly involved in the progression of human gliomas. © 2001 Wiley‐Liss, Inc.</description><subject>Astrocytoma - genetics</subject><subject>Astrocytoma - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Collagen - chemistry</subject><subject>DNA Primers - chemistry</subject><subject>Drug Combinations</subject><subject>Fibrin - metabolism</subject><subject>glioblastoma</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>HGF</subject><subject>HGF activator inhibitor type‐2</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>invasion</subject><subject>Laminin - chemistry</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Neurology</subject><subject>Proteoglycans - chemistry</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Serine Proteinase Inhibitors - genetics</subject><subject>Serine Proteinase Inhibitors - metabolism</subject><subject>Transfection</subject><subject>Trypsin Inhibitor, Kunitz Soybean</subject><subject>Tumors of the nervous system. Phacomatoses</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0EoktB4gmQL6BySGvHSRxzK6tCF1UCIThHE8fpujh2ajvb7o1H4L14C56EuLvScuEyM9J88_8j_Qi9pOSUEpKf6Rt5SlkhHqEFJYJnJKflY7SYVyTjlFVH6FkIN4RQWpLiKTqitGCMCb5Av7-qbpKqw-p-9CoE7Sx2PV6rEaKT26jwtXd3cY17kNF5PFe9gTRpu9atTlPcjurPz1_52WhAKhvB4Fb_mKy2-OTyfPWw-vL-7XyB19MAFl8b7VoDIboBwju8GkajJcTk3ScPG_V8pO0Ggt4o7J1R6amDVpL6VwRLZUx4jp70YIJ6se_H6PuHi2_Ly-zq88fV8vwqkyyvRda1hJaq5i0TVVn2soK6qtuSECZVVYKEghJGc1kJzmnORVfXqs151dYdr4ECO0Zvdrqjd7eTCrEZdEgfgFVuCg0nohIiL2fwZAdK70Lwqm9Grwfw24aSJgXXzME1KbgZfbXXnNpBdQdwn9QMvN4DECSY3oOVOhy4gtSkoEko23F32qjtfw2b1aflg_FfAba06Q</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>Hamasuna, Ryouichi</creator><creator>Kataoka, Hiroaki</creator><creator>Meng, Jing‐Yan</creator><creator>Itoh, Hiroshi</creator><creator>Moriyama, Takuzou</creator><creator>Wakisaka, Shinichiro</creator><creator>Koono, Masashi</creator><general>John Wiley & Sons, Inc</general><general>Wiley-Liss</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>20010801</creationdate><title>Reduced expression of hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) in human glioblastomas: Implication for anti‐invasive role of HAI‐2/PB in glioblastoma cells</title><author>Hamasuna, Ryouichi ; Kataoka, Hiroaki ; Meng, Jing‐Yan ; Itoh, Hiroshi ; Moriyama, Takuzou ; Wakisaka, Shinichiro ; Koono, Masashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3289-db015e87b39655fc6a868b5003ce65aca410312c69771279d88eb276b8d78a1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Astrocytoma - genetics</topic><topic>Astrocytoma - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Collagen - chemistry</topic><topic>DNA Primers - chemistry</topic><topic>Drug Combinations</topic><topic>Fibrin - metabolism</topic><topic>glioblastoma</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>HGF</topic><topic>HGF activator inhibitor type‐2</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>invasion</topic><topic>Laminin - chemistry</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Neoplasm Invasiveness</topic><topic>Neurology</topic><topic>Proteoglycans - chemistry</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Serine Endopeptidases - metabolism</topic><topic>Serine Proteinase Inhibitors - genetics</topic><topic>Serine Proteinase Inhibitors - metabolism</topic><topic>Transfection</topic><topic>Trypsin Inhibitor, Kunitz Soybean</topic><topic>Tumors of the nervous system. Phacomatoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamasuna, Ryouichi</creatorcontrib><creatorcontrib>Kataoka, Hiroaki</creatorcontrib><creatorcontrib>Meng, Jing‐Yan</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><creatorcontrib>Moriyama, Takuzou</creatorcontrib><creatorcontrib>Wakisaka, Shinichiro</creatorcontrib><creatorcontrib>Koono, Masashi</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>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamasuna, Ryouichi</au><au>Kataoka, Hiroaki</au><au>Meng, Jing‐Yan</au><au>Itoh, Hiroshi</au><au>Moriyama, Takuzou</au><au>Wakisaka, Shinichiro</au><au>Koono, Masashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced expression of hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) in human glioblastomas: Implication for anti‐invasive role of HAI‐2/PB in glioblastoma cells</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>93</volume><issue>3</issue><spage>339</spage><epage>345</epage><pages>339-345</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>Hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) is a serine proteinase inhibitor that contains 2 Kunitz‐domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI‐2/PB in human gliomas in vivo and the effects of HAI‐2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI‐2/PB mRNA was expressed in normal brain and in low‐grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI‐2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG‐1) were transiently transfected with an expression vector harboring human HAI‐2/PB cDNA. Subsequent analysis indicated that the expression of HAI‐2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI‐2/PB inhibited Matrigel invasion of U251 and YKG‐1 cells by 30% and 64%, respectively. This anti‐invasive effect appeared to be mediated primarily by the inhibitory activity of HAI‐2/PB against the serine proteinase‐dependent matrix degradation. These findings suggest that the reduced expression of HAI‐2/PB is possibly involved in the progression of human gliomas. © 2001 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11433397</pmid><doi>10.1002/ijc.1349</doi><tpages>7</tpages></addata></record> |
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| ispartof | International journal of cancer, 2001-08, Vol.93 (3), p.339-345 |
| issn | 0020-7136 1097-0215 |
| language | eng |
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| subjects | Astrocytoma - genetics Astrocytoma - metabolism Biological and medical sciences Blotting, Northern Brain Neoplasms - genetics Brain Neoplasms - metabolism Collagen - chemistry DNA Primers - chemistry Drug Combinations Fibrin - metabolism glioblastoma Glioblastoma - genetics Glioblastoma - metabolism Hepatocyte Growth Factor - metabolism HGF HGF activator inhibitor type‐2 Humans Immunoblotting invasion Laminin - chemistry Medical sciences Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Neoplasm Invasiveness Neurology Proteoglycans - chemistry Proto-Oncogene Proteins c-met - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA - metabolism RNA, Messenger - metabolism Serine Endopeptidases - metabolism Serine Proteinase Inhibitors - genetics Serine Proteinase Inhibitors - metabolism Transfection Trypsin Inhibitor, Kunitz Soybean Tumors of the nervous system. Phacomatoses |
| title | Reduced expression of hepatocyte growth factor activator inhibitor type‐2/placental bikunin (HAI‐2/PB) in human glioblastomas: Implication for anti‐invasive role of HAI‐2/PB in glioblastoma cells |
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