Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model
Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, littl...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-11, Vol.6 (11), p.e26075-e26075 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e26075 |
|---|---|
| container_issue | 11 |
| container_start_page | e26075 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Pépin, David Shao, Zhong-Qi Huppé, Geneviève Wakefield, Andrea Chu, Chee-Wui Sharif, Zahra Vanderhyden, Barbara C |
| description | Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer. |
| doi_str_mv | 10.1371/journal.pone.0026075 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1312113259</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476862982</galeid><doaj_id>oai_doaj_org_article_2e27b234476c473793294236ed45c294</doaj_id><sourcerecordid>A476862982</sourcerecordid><originalsourceid>FETCH-LOGICAL-c691t-63d837934ad441c9dbbd743b8913ddb6aee5a9ec6af035e096796ac1ac094aa03</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLgiI4Yz7atLkRlsWPwYUFv27DaZJ2MmaSMWmHnX9vZqe7TGUvpBcJJ8_7Jnmbk2XPMZpjWuH3Kz8EB3a-8U7PESIMVeWD7BRzSmaMIPrwaH6SPYlxhVBJa8YeZyeEYETqsjrNtl_BWvM7aONiXr7LWQ5O5RjlyrStDtr1JgG7HGyvQ76Bfuk3y1003vpud8P6rQ4JyeMQtmYLNjcu1VMZgkmjBCeT8lo73wVo-3ztlbZPs0ct2KifjeNZ9vPTxx8XX2aXV58XF-eXM8k47meMqppWnBagigJLrppGVQVtao6pUg0DrUvgWjJoES014qziDCQGiXgBgOhZ9vLgu7E-ijGyKDDFBGNKSp6IxYFQHlZiE8wawk54MOKm4EMnIPRGWi2IJlVDaFFUTBbV_lyEF4QyrYpSpmny-jDuNjRrrWRKL0UzMZ2uOLMUnd8KSjDjpE4Gb0aD4P8MOvZibaLU1oLTfoiCo5LVFNc4ka_-Ie-_3Eh1kM5vXOvTtnLvKc7TLWpGeE0SNb-HSp_SayPT82pNqk8EbyeCxPT6uu9giFEsvn_7f_bq15R9fcQudXp0y-jt0Bvv4hQsDqAMPsag27uMMRL77rhNQ-y7Q4zdkWQvjv_Pnei2HehfzvoKAA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1312113259</pqid></control><display><type>article</type><title>Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Pépin, David ; Shao, Zhong-Qi ; Huppé, Geneviève ; Wakefield, Andrea ; Chu, Chee-Wui ; Sharif, Zahra ; Vanderhyden, Barbara C</creator><contributor>Srivastava, Rakesh K.</contributor><creatorcontrib>Pépin, David ; Shao, Zhong-Qi ; Huppé, Geneviève ; Wakefield, Andrea ; Chu, Chee-Wui ; Sharif, Zahra ; Vanderhyden, Barbara C ; Srivastava, Rakesh K.</creatorcontrib><description>Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026075</identifier><identifier>PMID: 22102857</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Agar ; Angiogenesis ; Animals ; Antigens ; Ascites ; Bioindicators ; Biology ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biotechnology ; Cancer ; Cancer research ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Cell survival ; Colonies ; Colorectal cancer ; Diagnostic systems ; Disease ; Enzyme-Linked Immunosorbent Assay ; Enzymes ; Expression vectors ; Extracellular matrix ; Female ; Fluid ; Fluids ; Humans ; Immunoassay ; Kallikrein ; Kallikreins - metabolism ; Medical prognosis ; Medical research ; Medicine ; Metastasis ; Mice ; Mice, Nude ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - physiopathology ; Patient outcomes ; Pharmaceuticals ; Prostate cancer ; Proteins ; Secretion ; Serine ; Survival ; Survival Rate ; Tumor cell lines ; Tumor Cells, Cultured ; Tumorigenicity ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e26075-e26075</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Pépin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Pépin et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-63d837934ad441c9dbbd743b8913ddb6aee5a9ec6af035e096796ac1ac094aa03</citedby><cites>FETCH-LOGICAL-c691t-63d837934ad441c9dbbd743b8913ddb6aee5a9ec6af035e096796ac1ac094aa03</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/PMC3216928/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216928/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22102857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Srivastava, Rakesh K.</contributor><creatorcontrib>Pépin, David</creatorcontrib><creatorcontrib>Shao, Zhong-Qi</creatorcontrib><creatorcontrib>Huppé, Geneviève</creatorcontrib><creatorcontrib>Wakefield, Andrea</creatorcontrib><creatorcontrib>Chu, Chee-Wui</creatorcontrib><creatorcontrib>Sharif, Zahra</creatorcontrib><creatorcontrib>Vanderhyden, Barbara C</creatorcontrib><title>Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer.</description><subject>Aberration</subject><subject>Agar</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antigens</subject><subject>Ascites</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cell Adhesion</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell survival</subject><subject>Colonies</subject><subject>Colorectal cancer</subject><subject>Diagnostic systems</subject><subject>Disease</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Enzymes</subject><subject>Expression vectors</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Fluid</subject><subject>Fluids</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Kallikrein</subject><subject>Kallikreins - metabolism</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - physiopathology</subject><subject>Patient outcomes</subject><subject>Pharmaceuticals</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Secretion</subject><subject>Serine</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Tumor cell lines</subject><subject>Tumor Cells, Cultured</subject><subject>Tumorigenicity</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgiI4Yz7atLkRlsWPwYUFv27DaZJ2MmaSMWmHnX9vZqe7TGUvpBcJJ8_7Jnmbk2XPMZpjWuH3Kz8EB3a-8U7PESIMVeWD7BRzSmaMIPrwaH6SPYlxhVBJa8YeZyeEYETqsjrNtl_BWvM7aONiXr7LWQ5O5RjlyrStDtr1JgG7HGyvQ76Bfuk3y1003vpud8P6rQ4JyeMQtmYLNjcu1VMZgkmjBCeT8lo73wVo-3ztlbZPs0ct2KifjeNZ9vPTxx8XX2aXV58XF-eXM8k47meMqppWnBagigJLrppGVQVtao6pUg0DrUvgWjJoES014qziDCQGiXgBgOhZ9vLgu7E-ijGyKDDFBGNKSp6IxYFQHlZiE8wawk54MOKm4EMnIPRGWi2IJlVDaFFUTBbV_lyEF4QyrYpSpmny-jDuNjRrrWRKL0UzMZ2uOLMUnd8KSjDjpE4Gb0aD4P8MOvZibaLU1oLTfoiCo5LVFNc4ka_-Ie-_3Eh1kM5vXOvTtnLvKc7TLWpGeE0SNb-HSp_SayPT82pNqk8EbyeCxPT6uu9giFEsvn_7f_bq15R9fcQudXp0y-jt0Bvv4hQsDqAMPsag27uMMRL77rhNQ-y7Q4zdkWQvjv_Pnei2HehfzvoKAA</recordid><startdate>20111115</startdate><enddate>20111115</enddate><creator>Pépin, David</creator><creator>Shao, Zhong-Qi</creator><creator>Huppé, Geneviève</creator><creator>Wakefield, Andrea</creator><creator>Chu, Chee-Wui</creator><creator>Sharif, Zahra</creator><creator>Vanderhyden, Barbara C</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>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>20111115</creationdate><title>Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model</title><author>Pépin, David ; Shao, Zhong-Qi ; Huppé, Geneviève ; Wakefield, Andrea ; Chu, Chee-Wui ; Sharif, Zahra ; Vanderhyden, Barbara C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-63d837934ad441c9dbbd743b8913ddb6aee5a9ec6af035e096796ac1ac094aa03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aberration</topic><topic>Agar</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antigens</topic><topic>Ascites</topic><topic>Bioindicators</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Cell Adhesion</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell survival</topic><topic>Colonies</topic><topic>Colorectal cancer</topic><topic>Diagnostic systems</topic><topic>Disease</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Enzymes</topic><topic>Expression vectors</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Fluid</topic><topic>Fluids</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Kallikrein</topic><topic>Kallikreins - metabolism</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - physiopathology</topic><topic>Patient outcomes</topic><topic>Pharmaceuticals</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Secretion</topic><topic>Serine</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Tumor cell lines</topic><topic>Tumor Cells, Cultured</topic><topic>Tumorigenicity</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pépin, David</creatorcontrib><creatorcontrib>Shao, Zhong-Qi</creatorcontrib><creatorcontrib>Huppé, Geneviève</creatorcontrib><creatorcontrib>Wakefield, Andrea</creatorcontrib><creatorcontrib>Chu, Chee-Wui</creatorcontrib><creatorcontrib>Sharif, Zahra</creatorcontrib><creatorcontrib>Vanderhyden, Barbara C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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>Pépin, David</au><au>Shao, Zhong-Qi</au><au>Huppé, Geneviève</au><au>Wakefield, Andrea</au><au>Chu, Chee-Wui</au><au>Sharif, Zahra</au><au>Vanderhyden, Barbara C</au><au>Srivastava, Rakesh K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-15</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e26075</spage><epage>e26075</epage><pages>e26075-e26075</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22102857</pmid><doi>10.1371/journal.pone.0026075</doi><tpages>e26075</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-11, Vol.6 (11), p.e26075-e26075 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312113259 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Agar Angiogenesis Animals Antigens Ascites Bioindicators Biology Biomarkers Biomarkers, Tumor - metabolism Biotechnology Cancer Cancer research Cell Adhesion Cell Movement Cell Proliferation Cell survival Colonies Colorectal cancer Diagnostic systems Disease Enzyme-Linked Immunosorbent Assay Enzymes Expression vectors Extracellular matrix Female Fluid Fluids Humans Immunoassay Kallikrein Kallikreins - metabolism Medical prognosis Medical research Medicine Metastasis Mice Mice, Nude Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - metabolism Ovarian Neoplasms - mortality Ovarian Neoplasms - physiopathology Patient outcomes Pharmaceuticals Prostate cancer Proteins Secretion Serine Survival Survival Rate Tumor cell lines Tumor Cells, Cultured Tumorigenicity Tumors Xenograft Model Antitumor Assays Xenografts |
| title | Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T17%3A09%3A05IST&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=Kallikreins%205,%206%20and%2010%20differentially%20alter%20pathophysiology%20and%20overall%20survival%20in%20an%20ovarian%20cancer%20xenograft%20model&rft.jtitle=PloS%20one&rft.au=P%C3%A9pin,%20David&rft.date=2011-11-15&rft.volume=6&rft.issue=11&rft.spage=e26075&rft.epage=e26075&rft.pages=e26075-e26075&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0026075&rft_dat=%3Cgale_plos_%3EA476862982%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=1312113259&rft_id=info:pmid/22102857&rft_galeid=A476862982&rft_doaj_id=oai_doaj_org_article_2e27b234476c473793294236ed45c294&rfr_iscdi=true |