Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma

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dc.citation.firstpagee67054en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitlePLoS Oneen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorBaird, Brandi N.en_US
dc.contributor.authorSchliekelman, Mark J.en_US
dc.contributor.authorAhn, Young-Hoen_US
dc.contributor.authorChen, Yulongen_US
dc.contributor.authorRoybal, Jonathon D.en_US
dc.contributor.authorGill, Bartley J.en_US
dc.contributor.authorMishra, Dhruva K.en_US
dc.contributor.authorErez, Baruchen_US
dc.contributor.authorOﾒReilly, Michaelen_US
dc.contributor.authorYang, Yananen_US
dc.contributor.authorPatel, Mayurien_US
dc.contributor.authorLiu, Xinen_US
dc.contributor.authorThilaganathan, Nishanen_US
dc.contributor.authorLarina, Irina V.en_US
dc.contributor.authorDickinson, Mary E.en_US
dc.contributor.authorWest, Jennifer L.en_US
dc.contributor.authorGibbons, Don L.en_US
dc.contributor.authorLiu, Diane D.en_US
dc.contributor.authorKim, Min P.en_US
dc.contributor.authorHicks, John M.en_US
dc.contributor.authorWistuba, Ignacio I.en_US
dc.contributor.authorHanash, Samir M.en_US
dc.contributor.authorKurie, Jonathan M.en_US
dc.date.accessioned2013-06-19T18:37:45Zen_US
dc.date.available2013-06-19T18:37:45Zen_US
dc.date.issued2013en_US
dc.description.abstractThe extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-offunction experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wildtype littermates, implying that malignant progression was dependent specifically upon tumor cellderived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We concludeen_US
dc.embargo.termsnoneen_US
dc.identifier.citationBaird, Brandi N., Schliekelman, Mark J., Ahn, Young-Ho, et al.. "Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma." <i>PLoS One,</i> 8, no. 6 (2013) Public Library of Science: e67054. http://dx.doi.org/10.1371/journal.pone.0067054.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0067054en_US
dc.identifier.urihttps://hdl.handle.net/1911/71339en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleFibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinomaen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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