Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

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dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.authorHall-Manning, Kellien
dc.contributor.authorKing, Jamie N.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorDebinski, Waldemaren
dc.contributor.authorElankumaran, Subbiahen
dc.date.accessioned2019-01-31T16:06:37Zen
dc.date.available2019-01-31T16:06:37Zen
dc.date.issued2017-04-12en
dc.description.abstractBackground: The expression of the urokinase plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA), have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs. Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real-time quantitative polymerase chain reaction analyses, and by the assay of the activity of uPA using casein–plasminogen zymography. Results: Expression of uPAR was observed in multiple tumoral microenvironmental niches, including neoplastic cells, stroma, and the vasculature of canine brain tumors. Relative to normal brain tissues, uPAR protein and mRNA expression were significantly greater in canine meningiomas, gliomas, and choroid plexus tumors. Increased activity of uPA was documented in all tumor types. Conclusions: uPAR is overexpressed and uPA activity increased in canine meningiomas, gliomas, and choroid plexus tumors. This study illustrates the potential of uPAR/uPA molecularly targeted approaches for canine brain tumor therapeutics and reinforces the translational significance of canines with spontaneous brain tumors as models for human disease.en
dc.description.sponsorshipPortions of this study were funded by the Wallace H. Coulter Foundation Career Grant, the Virginia Biosciences Health Research Corporation, the Virginia Veterinary Memorial Fund, R01 CA139099/CA/NCI NIH HHS, and R21 AI070528/AI/NIAID NIH HHS. We acknowledge and appreciate the contributions of our friend and colleague,Dr Subbiah Elankumaran, who passed away on September 2, 2015, prior to completion of the article.en
dc.description.versionPublished versionen
dc.format.extent9 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.2147/ott.s132964en
dc.identifier.urihttp://hdl.handle.net/10919/87094en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherDove Pressen
dc.rightsCreative Commons Attribution-NonCommercial 3.0 United Statesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/en
dc.subjectbrain tumoren
dc.subjectneuro-oncologyen
dc.subjectdogen
dc.subjectanimal modelen
dc.subjectproteaseen
dc.subjectmeningiomaen
dc.subjectgliomaen
dc.titleExpression and activity of the urokinase plasminogen activator system in canine primary brain tumorsen
dc.title.serialOncoTargets and Therapyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Small Animal Clinical Sciences
Destination Area: Adaptive Brain and Behavior (ABB)