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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Matrix Metalloproteinase-19 Promotes Metastatic Behavior <italic>In Vitro</italic>
and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer</title>
<author><name sortKey="Yu, Guoying" sort="Yu, Guoying" uniqKey="Yu G" first="Guoying" last="Yu">Guoying Yu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Herazo Maya, Jose D" sort="Herazo Maya, Jose D" uniqKey="Herazo Maya J" first="Jose D." last="Herazo-Maya">Jose D. Herazo-Maya</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nukui, Tomoko" sort="Nukui, Tomoko" uniqKey="Nukui T" first="Tomoko" last="Nukui">Tomoko Nukui</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Romkes, Marjorie" sort="Romkes, Marjorie" uniqKey="Romkes M" first="Marjorie" last="Romkes">Marjorie Romkes</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Parwani, Anil" sort="Parwani, Anil" uniqKey="Parwani A" first="Anil" last="Parwani">Anil Parwani</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Juan Guardela, Brenda M" sort="Juan Guardela, Brenda M" uniqKey="Juan Guardela B" first="Brenda M." last="Juan-Guardela">Brenda M. Juan-Guardela</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robertson, Jennifer" sort="Robertson, Jennifer" uniqKey="Robertson J" first="Jennifer" last="Robertson">Jennifer Robertson</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gauldie, Jack" sort="Gauldie, Jack" uniqKey="Gauldie J" first="Jack" last="Gauldie">Jack Gauldie</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siegfried, Jill M" sort="Siegfried, Jill M" uniqKey="Siegfried J" first="Jill M." last="Siegfried">Jill M. Siegfried</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kass, Daniel J" sort="Kass, Daniel J" uniqKey="Kass D" first="Daniel J." last="Kass">Daniel J. Kass</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25250855</idno>
<idno type="pmc">4299607</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299607</idno>
<idno type="RBID">PMC:4299607</idno>
<idno type="doi">10.1164/rccm.201310-1903OC</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000872</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000872</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Matrix Metalloproteinase-19 Promotes Metastatic Behavior <italic>In Vitro</italic>
and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer</title>
<author><name sortKey="Yu, Guoying" sort="Yu, Guoying" uniqKey="Yu G" first="Guoying" last="Yu">Guoying Yu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Herazo Maya, Jose D" sort="Herazo Maya, Jose D" uniqKey="Herazo Maya J" first="Jose D." last="Herazo-Maya">Jose D. Herazo-Maya</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nukui, Tomoko" sort="Nukui, Tomoko" uniqKey="Nukui T" first="Tomoko" last="Nukui">Tomoko Nukui</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Romkes, Marjorie" sort="Romkes, Marjorie" uniqKey="Romkes M" first="Marjorie" last="Romkes">Marjorie Romkes</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Parwani, Anil" sort="Parwani, Anil" uniqKey="Parwani A" first="Anil" last="Parwani">Anil Parwani</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Juan Guardela, Brenda M" sort="Juan Guardela, Brenda M" uniqKey="Juan Guardela B" first="Brenda M." last="Juan-Guardela">Brenda M. Juan-Guardela</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robertson, Jennifer" sort="Robertson, Jennifer" uniqKey="Robertson J" first="Jennifer" last="Robertson">Jennifer Robertson</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gauldie, Jack" sort="Gauldie, Jack" uniqKey="Gauldie J" first="Jack" last="Gauldie">Jack Gauldie</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siegfried, Jill M" sort="Siegfried, Jill M" uniqKey="Siegfried J" first="Jill M." last="Siegfried">Jill M. Siegfried</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kass, Daniel J" sort="Kass, Daniel J" uniqKey="Kass D" first="Daniel J." last="Kass">Daniel J. Kass</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Respiratory and Critical Care Medicine</title>
<idno type="ISSN">1073-449X</idno>
<idno type="eISSN">1535-4970</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><bold>Rationale:</bold>
Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Matrix metalloproteinases (MMPs) have been implicated in the development and progression of lung cancer, but their role in the molecular pathogenesis of lung cancer remains unclear. We have found that MMP19, a relatively novel member of the MMP family, is overexpressed in lung tumors when compared with control subjects.</p>
<p><bold>Objectives:</bold>
To test the hypothesis that MMP19 plays a significant role in the development and progression of non–small cell lung cancer (NSCLC).</p>
<p><bold>Methods:</bold>
We have analyzed lung cancer gene expression data, immunostained lung tumors for MMP19, and performed <italic>in vitro</italic>
assays to test the effects of MMP19 in NSCLC cells.</p>
<p><bold>Measurements and Main Results:</bold>
We found that MMP19 gene and protein expression is increased in lung cancer tumors compared with adjacent and histologically normal lung tissues. In three independent datasets, increased MMP19 gene expression conferred a poorer prognosis in NSCLC. <italic>In vitro</italic>
, we found that overexpression of MMP19 promotes epithelial–mesenchymal transition, migration, and invasiveness in multiple NSCLC cell lines. Overexpression of MMP19 with a mutation at the catalytic site did not impair epithelial–mesenchymal transition or expression of prometastasis genes. We also found that miR-30 isoforms, a microRNA family predicted to target MMP19, is markedly down-regulated in human lung cancer and regulates MMP19 expression.</p>
<p><bold>Conclusions:</bold>
Taken together, these findings suggest that MMP19 is associated with the development and progression of NSCLC and may be a potential biomarker of disease severity and outcome.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Respir Crit Care Med</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Respir. Crit. Care Med</journal-id>
<journal-id journal-id-type="publisher-id">ajrccm</journal-id>
<journal-title-group><journal-title>American Journal of Respiratory and Critical Care Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1073-449X</issn>
<issn pub-type="epub">1535-4970</issn>
<publisher><publisher-name>American Thoracic Society</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25250855</article-id>
<article-id pub-id-type="pmc">4299607</article-id>
<article-id pub-id-type="publisher-manuscript">201310-1903OC</article-id>
<article-id pub-id-type="doi">10.1164/rccm.201310-1903OC</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject>
<subj-group><subject>Lung Cancer and Oncologic Disorders</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Matrix Metalloproteinase-19 Promotes Metastatic Behavior <italic>In Vitro</italic>
and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Yu</surname>
<given-names>Guoying</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Herazo-Maya</surname>
<given-names>Jose D.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nukui</surname>
<given-names>Tomoko</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Romkes</surname>
<given-names>Marjorie</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Parwani</surname>
<given-names>Anil</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Juan-Guardela</surname>
<given-names>Brenda M.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robertson</surname>
<given-names>Jennifer</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gauldie</surname>
<given-names>Jack</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siegfried</surname>
<given-names>Jill M.</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaminski</surname>
<given-names>Naftali</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Kass</surname>
<given-names>Daniel J.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>7</sup>
</xref>
<xref ref-type="aff" rid="aff8"><sup>8</sup>
</xref>
</contrib>
<aff id="aff1"><label><sup>1</sup>
</label>
Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut</aff>
<aff id="aff2"><label><sup>2</sup>
</label>
Division of Hematology and Oncology</aff>
<aff id="aff3"><label><sup>6</sup>
</label>
Division of Pulmonary, Allergy, and Critical Care Medicine, and</aff>
<aff id="aff4"><label><sup>7</sup>
</label>
Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Department of Medicine, and</aff>
<aff id="aff5"><label><sup>3</sup>
</label>
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania</aff>
<aff id="aff6"><label><sup>4</sup>
</label>
Department of Pathology and Laboratory Medicine, McMaster University, Hamilton, Ontario, Canada</aff>
<aff id="aff7"><label><sup>5</sup>
</label>
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota; and</aff>
<aff id="aff8"><label><sup>8</sup>
</label>
VA Pittsburgh Health System, Pittsburgh, Pennsylvania</aff>
</contrib-group>
<author-notes><corresp>Correspondence and requests for reprints should be addressed to Daniel J. Kass, M.D., UPMC Montefiore, NW 628, 3459 Fifth Avenue, Pittsburgh, PA 15213. E-mail: <email xlink:href="kassd2@upmc.edu">kassd2@upmc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="epub-ppub"><day>1</day>
<month>10</month>
<year>2014</year>
<pmc-comment>string-date: October 1, 2014</pmc-comment>
</pub-date>
<pmc-comment>Fake epub and ppub dates generated by PMC from publisher
pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="epub"><day>1</day>
<month>10</month>
<year>2014</year>
<pmc-comment>string-date: October 1, 2014</pmc-comment>
</pub-date>
<pub-date pub-type="ppub"><day>1</day>
<month>10</month>
<year>2014</year>
<pmc-comment>string-date: October 1, 2014</pmc-comment>
</pub-date>
<volume>190</volume>
<issue>7</issue>
<fpage>780</fpage>
<lpage>790</lpage>
<history><date date-type="received"><day>30</day>
<month>10</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>30</day>
<month>8</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014 by the American Thoracic Society</copyright-statement>
<copyright-year>2014</copyright-year>
</permissions>
<self-uri content-type="pdf" xlink:href="rccm.201310-1903OC.pdf"></self-uri>
<abstract><p><bold>Rationale:</bold>
Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Matrix metalloproteinases (MMPs) have been implicated in the development and progression of lung cancer, but their role in the molecular pathogenesis of lung cancer remains unclear. We have found that MMP19, a relatively novel member of the MMP family, is overexpressed in lung tumors when compared with control subjects.</p>
<p><bold>Objectives:</bold>
To test the hypothesis that MMP19 plays a significant role in the development and progression of non–small cell lung cancer (NSCLC).</p>
<p><bold>Methods:</bold>
We have analyzed lung cancer gene expression data, immunostained lung tumors for MMP19, and performed <italic>in vitro</italic>
assays to test the effects of MMP19 in NSCLC cells.</p>
<p><bold>Measurements and Main Results:</bold>
We found that MMP19 gene and protein expression is increased in lung cancer tumors compared with adjacent and histologically normal lung tissues. In three independent datasets, increased MMP19 gene expression conferred a poorer prognosis in NSCLC. <italic>In vitro</italic>
, we found that overexpression of MMP19 promotes epithelial–mesenchymal transition, migration, and invasiveness in multiple NSCLC cell lines. Overexpression of MMP19 with a mutation at the catalytic site did not impair epithelial–mesenchymal transition or expression of prometastasis genes. We also found that miR-30 isoforms, a microRNA family predicted to target MMP19, is markedly down-regulated in human lung cancer and regulates MMP19 expression.</p>
<p><bold>Conclusions:</bold>
Taken together, these findings suggest that MMP19 is associated with the development and progression of NSCLC and may be a potential biomarker of disease severity and outcome.</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>MMP19</kwd>
<kwd>epithelial–mesenchymal transition</kwd>
<kwd>metastasis</kwd>
<kwd>non–small cell lung cancer</kwd>
<kwd>miR-30</kwd>
</kwd-group>
<counts><fig-count count="7"></fig-count>
<table-count count="0"></table-count>
<page-count count="11"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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