The role of matrix metalloproteinase in the intimal sarcoma-like cells derived from endarterectomized tissues from a chronic thromboembolic pulmonary hypertension patient
Sarcoma-like cells (SCLs) were derived from endarterectomized tissue of a single chronic thromboembolic pulmonary hypertension (CTEPH) patient during incubation of those thrombi at second passage as described at our previous report. These cells had malignant potential, with an increased expression o...
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| description | Sarcoma-like cells (SCLs) were derived from endarterectomized tissue of a single chronic thromboembolic pulmonary hypertension (CTEPH) patient during incubation of those thrombi at second passage as described at our previous report. These cells had malignant potential, with an increased expression of matrix metalloproteinase-14 (MMP-14), leading to tumor emboli within pulmonary arteries in in vivo studies. The purpose of this study was to perform a more detailed evaluation of the characteristics of SCLs, and to elucidate the role of the increased expression of MMP-14 expression in the growth and death of these cells. In order to elucidate the characteristics of SCLs and to confirm the protein expression of MMP-14, three-dimentional culture, invasion assays, a Western blot analysis and immunohistochemical studies were performed. To examine the role of MMP-14 in tumorigenesis, the metalloproteinase inhibitor, batimastat, was administered to SCID mice which were subcutaneously injected with SCLs. Those mice were sacrificed on day 14 and the tumor volume was evaluated. A Western blot analysis showed the increased expression of MMP-14 in comparison to the expression in lung adenocarcinoma cells (A549). Immunohistochemistry showed that SCLs were positive for vimentin, MMP-14, MMP-2 and CD44. However, endothelial markers, such as CD31 and von Willebrand factor (vWF), were negative. The in vivo studies demonstrated that batimastat could suppress the growth of the subcutaneous tumors formed by the SCLs. This study suggested that MMPs had critical roles on the pathological activities of SCLs and that batimastat might have anti-proliferative and anti-invasive effects on these cells. |
| doi_str_mv | 10.1371/journal.pone.0087489 |
| format | Article |
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These cells had malignant potential, with an increased expression of matrix metalloproteinase-14 (MMP-14), leading to tumor emboli within pulmonary arteries in in vivo studies. The purpose of this study was to perform a more detailed evaluation of the characteristics of SCLs, and to elucidate the role of the increased expression of MMP-14 expression in the growth and death of these cells. In order to elucidate the characteristics of SCLs and to confirm the protein expression of MMP-14, three-dimentional culture, invasion assays, a Western blot analysis and immunohistochemical studies were performed. To examine the role of MMP-14 in tumorigenesis, the metalloproteinase inhibitor, batimastat, was administered to SCID mice which were subcutaneously injected with SCLs. Those mice were sacrificed on day 14 and the tumor volume was evaluated. A Western blot analysis showed the increased expression of MMP-14 in comparison to the expression in lung adenocarcinoma cells (A549). Immunohistochemistry showed that SCLs were positive for vimentin, MMP-14, MMP-2 and CD44. However, endothelial markers, such as CD31 and von Willebrand factor (vWF), were negative. The in vivo studies demonstrated that batimastat could suppress the growth of the subcutaneous tumors formed by the SCLs. This study suggested that MMPs had critical roles on the pathological activities of SCLs and that batimastat might have anti-proliferative and anti-invasive effects on these cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0087489</identifier><identifier>PMID: 24489925</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Analysis ; Animal tissues ; Animals ; Arteries ; Biology ; Blotting, Western ; Cancer ; CD44 antigen ; Cell adhesion & migration ; Cell culture ; Cell Culture Techniques ; Embolisms ; Gelatinase A ; Growth factors ; Humans ; Hypertension ; Hypertension, Pulmonary - enzymology ; Hypertension, Pulmonary - metabolism ; Immunoglobulins ; Immunohistochemistry ; In vivo methods and tests ; Intermediate filament proteins ; Invasiveness ; Kinases ; Lung cancer ; Lungs ; Matrix metalloproteinase ; Matrix Metalloproteinase 14 - metabolism ; Matrix Metalloproteinase 14 - physiology ; Medicine ; Metalloproteinase ; Metastasis ; Mice ; Mice, SCID ; Neoplasm Invasiveness ; Pulmonary arteries ; Pulmonary artery ; Pulmonary Artery - pathology ; Pulmonary embolisms ; Pulmonary hypertension ; Sarcoma ; Sarcoma - pathology ; Thromboembolism ; Thrombosis ; Tumor Cells, Cultured ; Tumorigenesis ; Tumors ; Veins & arteries ; Vimentin ; Von Willebrand factor</subject><ispartof>PloS one, 2014-01, Vol.9 (1), p.e87489-e87489</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Jujo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Jujo et al 2014 Jujo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-41a34c7c3f196a9ca40603161b6139fe406ef3e3f5627b2084f5d86534dd54cf3</citedby><cites>FETCH-LOGICAL-c758t-41a34c7c3f196a9ca40603161b6139fe406ef3e3f5627b2084f5d86534dd54cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905027/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905027/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24489925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jujo, Takayuki</creatorcontrib><creatorcontrib>Sakao, Seiichiro</creatorcontrib><creatorcontrib>Tsukahara, Masanori</creatorcontrib><creatorcontrib>Kantake, Masashi</creatorcontrib><creatorcontrib>Kantake, Seiji</creatorcontrib><creatorcontrib>Maruoka, Miki</creatorcontrib><creatorcontrib>Tanabe, Nobuhiro</creatorcontrib><creatorcontrib>Masuda, Masahisa</creatorcontrib><creatorcontrib>Tatsumi, Koichiro</creatorcontrib><title>The role of matrix metalloproteinase in the intimal sarcoma-like cells derived from endarterectomized tissues from a chronic thromboembolic pulmonary hypertension patient</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sarcoma-like cells (SCLs) were derived from endarterectomized tissue of a single chronic thromboembolic pulmonary hypertension (CTEPH) patient during incubation of those thrombi at second passage as described at our previous report. These cells had malignant potential, with an increased expression of matrix metalloproteinase-14 (MMP-14), leading to tumor emboli within pulmonary arteries in in vivo studies. The purpose of this study was to perform a more detailed evaluation of the characteristics of SCLs, and to elucidate the role of the increased expression of MMP-14 expression in the growth and death of these cells. In order to elucidate the characteristics of SCLs and to confirm the protein expression of MMP-14, three-dimentional culture, invasion assays, a Western blot analysis and immunohistochemical studies were performed. To examine the role of MMP-14 in tumorigenesis, the metalloproteinase inhibitor, batimastat, was administered to SCID mice which were subcutaneously injected with SCLs. Those mice were sacrificed on day 14 and the tumor volume was evaluated. A Western blot analysis showed the increased expression of MMP-14 in comparison to the expression in lung adenocarcinoma cells (A549). Immunohistochemistry showed that SCLs were positive for vimentin, MMP-14, MMP-2 and CD44. However, endothelial markers, such as CD31 and von Willebrand factor (vWF), were negative. The in vivo studies demonstrated that batimastat could suppress the growth of the subcutaneous tumors formed by the SCLs. 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metabolism</subject><subject>Matrix Metalloproteinase 14 - physiology</subject><subject>Medicine</subject><subject>Metalloproteinase</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Neoplasm Invasiveness</subject><subject>Pulmonary arteries</subject><subject>Pulmonary artery</subject><subject>Pulmonary Artery - pathology</subject><subject>Pulmonary embolisms</subject><subject>Pulmonary hypertension</subject><subject>Sarcoma</subject><subject>Sarcoma - pathology</subject><subject>Thromboembolism</subject><subject>Thrombosis</subject><subject>Tumor Cells, Cultured</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Veins & arteries</subject><subject>Vimentin</subject><subject>Von Willebrand factor</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk21rFDEQxxdRbK1-A9GAIPrizuwm-_RGKMWHg0JBq29DLju5Tc0m2yRbWj-Sn9K53rXcSV_IsiQz-c0_mUkmy17mdJ6zOv9w4afgpJ2P3sGc0qbmTfsoO8xbVsyqgrLHO_OD7FmMF5SWrKmqp9lBwRFui_Iw-3PeAwneAvGaDDIFc00GSNJaPwafwDgZgRhHUr8ekhmkJVEG5Qc5s-YXEAXWRtJBMFfQER38QMB1MiQIoJIfzG90JxPjBHGzLInqg3dGoSjaSw_4WzTHyQ7eyXBD-psRUMFF4x0ZZTLg0vPsiZY2wovteJT9-Pzp_OTr7PTsy-Lk-HSm6rJJM55LxlWtmM7bSrZKclpRllf5sspZqwFN0AyYLquiXha04brsmqpkvOtKrjQ7yl5vdEfro9iWOYqct0VRs5ZXSCw2ROflhRgDFiXcCC-NuHX4sBKYv1EWBMuXDSuXnUR13jLaMM7bRmkqAbSSJWp93O42LQfoFCYapN0T3V9xphcrfyVYS0uKBzrK3m0Fgr_EGicxmLi-FOnAT7fn5ozWtKWIvvkHfTi7LbWSmIBx2uO-ai0qjnndNKyit9T8AQq_Dgaj8E1qg_69gPd7AcgkuE4rOcUoFt-__T979nOffbvD9iBt6qO3U8KnE_dBvgFV8DEG0PdFzqlYt9RdNcS6pcS2pTDs1e4F3Qfd9RD7C2vmIL8</recordid><startdate>20140128</startdate><enddate>20140128</enddate><creator>Jujo, Takayuki</creator><creator>Sakao, Seiichiro</creator><creator>Tsukahara, Masanori</creator><creator>Kantake, Masashi</creator><creator>Kantake, Seiji</creator><creator>Maruoka, Miki</creator><creator>Tanabe, Nobuhiro</creator><creator>Masuda, Masahisa</creator><creator>Tatsumi, Koichiro</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140128</creationdate><title>The role of matrix metalloproteinase in the intimal sarcoma-like cells derived from endarterectomized tissues from a chronic thromboembolic pulmonary hypertension patient</title><author>Jujo, Takayuki ; Sakao, Seiichiro ; Tsukahara, Masanori ; Kantake, Masashi ; Kantake, Seiji ; Maruoka, Miki ; Tanabe, Nobuhiro ; Masuda, Masahisa ; Tatsumi, Koichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-41a34c7c3f196a9ca40603161b6139fe406ef3e3f5627b2084f5d86534dd54cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenocarcinoma</topic><topic>Analysis</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Arteries</topic><topic>Biology</topic><topic>Blotting, Western</topic><topic>Cancer</topic><topic>CD44 antigen</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell Culture Techniques</topic><topic>Embolisms</topic><topic>Gelatinase A</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension, Pulmonary - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jujo, Takayuki</au><au>Sakao, Seiichiro</au><au>Tsukahara, Masanori</au><au>Kantake, Masashi</au><au>Kantake, Seiji</au><au>Maruoka, Miki</au><au>Tanabe, Nobuhiro</au><au>Masuda, Masahisa</au><au>Tatsumi, Koichiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of matrix metalloproteinase in the intimal sarcoma-like cells derived from endarterectomized tissues from a chronic thromboembolic pulmonary hypertension patient</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-01-28</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>e87489</spage><epage>e87489</epage><pages>e87489-e87489</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sarcoma-like cells (SCLs) were derived from endarterectomized tissue of a single chronic thromboembolic pulmonary hypertension (CTEPH) patient during incubation of those thrombi at second passage as described at our previous report. These cells had malignant potential, with an increased expression of matrix metalloproteinase-14 (MMP-14), leading to tumor emboli within pulmonary arteries in in vivo studies. The purpose of this study was to perform a more detailed evaluation of the characteristics of SCLs, and to elucidate the role of the increased expression of MMP-14 expression in the growth and death of these cells. In order to elucidate the characteristics of SCLs and to confirm the protein expression of MMP-14, three-dimentional culture, invasion assays, a Western blot analysis and immunohistochemical studies were performed. To examine the role of MMP-14 in tumorigenesis, the metalloproteinase inhibitor, batimastat, was administered to SCID mice which were subcutaneously injected with SCLs. Those mice were sacrificed on day 14 and the tumor volume was evaluated. A Western blot analysis showed the increased expression of MMP-14 in comparison to the expression in lung adenocarcinoma cells (A549). Immunohistochemistry showed that SCLs were positive for vimentin, MMP-14, MMP-2 and CD44. However, endothelial markers, such as CD31 and von Willebrand factor (vWF), were negative. The in vivo studies demonstrated that batimastat could suppress the growth of the subcutaneous tumors formed by the SCLs. This study suggested that MMPs had critical roles on the pathological activities of SCLs and that batimastat might have anti-proliferative and anti-invasive effects on these cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24489925</pmid><doi>10.1371/journal.pone.0087489</doi><tpages>e87489</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1492273946 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adenocarcinoma Analysis Animal tissues Animals Arteries Biology Blotting, Western Cancer CD44 antigen Cell adhesion & migration Cell culture Cell Culture Techniques Embolisms Gelatinase A Growth factors Humans Hypertension Hypertension, Pulmonary - enzymology Hypertension, Pulmonary - metabolism Immunoglobulins Immunohistochemistry In vivo methods and tests Intermediate filament proteins Invasiveness Kinases Lung cancer Lungs Matrix metalloproteinase Matrix Metalloproteinase 14 - metabolism Matrix Metalloproteinase 14 - physiology Medicine Metalloproteinase Metastasis Mice Mice, SCID Neoplasm Invasiveness Pulmonary arteries Pulmonary artery Pulmonary Artery - pathology Pulmonary embolisms Pulmonary hypertension Sarcoma Sarcoma - pathology Thromboembolism Thrombosis Tumor Cells, Cultured Tumorigenesis Tumors Veins & arteries Vimentin Von Willebrand factor |
| title | The role of matrix metalloproteinase in the intimal sarcoma-like cells derived from endarterectomized tissues from a chronic thromboembolic pulmonary hypertension patient |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T19%3A59%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20role%20of%20matrix%20metalloproteinase%20in%20the%20intimal%20sarcoma-like%20cells%20derived%20from%20endarterectomized%20tissues%20from%20a%20chronic%20thromboembolic%20pulmonary%20hypertension%20patient&rft.jtitle=PloS%20one&rft.au=Jujo,%20Takayuki&rft.date=2014-01-28&rft.volume=9&rft.issue=1&rft.spage=e87489&rft.epage=e87489&rft.pages=e87489-e87489&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0087489&rft_dat=%3Cgale_plos_%3EA478836046%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1492273946&rft_id=info:pmid/24489925&rft_galeid=A478836046&rft_doaj_id=oai_doaj_org_article_31b835bda4dd4930834498cf0aeefca5&rfr_iscdi=true |