Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model

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dc.contributor.authorCornelison, R. Chaseen
dc.contributor.authorBrennan, Caroline E.en
dc.contributor.authorKingsmore, Kathryn M.en
dc.contributor.authorMunson, Jennifer M.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2018-11-19T13:32:19Zen
dc.date.available2018-11-19T13:32:19Zen
dc.date.issued2019-11-18en
dc.description.abstractGlioblastoma is the most common and malignant form of brain cancer. Its invasive nature limits treatment efficacy and promotes inevitable recurrence. Previous in vitro studies showed that interstitial fluid flow, a factor characteristically increased in cancer, increases glioma cell invasion through CXCR4- CXCL12 signaling. It is currently unknown if these effects translate in vivo. We used the therapeutic technique of convection enhanced delivery (CED) to test if convective flow alters glioma invasion in a syngeneic GL261 mouse model of glioblastoma. The GL261 cell line was flow responsive in vitro, dependent upon CXCR4 and CXCL12. Additionally, transplanting GL261 intracranially increased the populations of CXCR4+ and double positive cells versus 3D culture. We showed that inducing convective flow within implanted tumors indeed increased invasion over untreated controls, and administering the CXCR4 antagonist AMD3100 (5 mg/kg) effectively eliminated this response. These data confirm that glioma invasion is stimulated by convective flow in vivo and depends on CXCR4 signaling. We also showed that expression of CXCR4 and CXCL12 is increased in patients having received standard therapy, when CED might be elected. Hence, targeting flow-stimulated invasion may prove beneficial as a second line of therapy, particularly in patients chosen to receive treatment by convection enhanced delivery.en
dc.description.sponsorshipFunding to JMM through ACS-IRG-81-001-29 and R01CA222563 and KMK through NSF GFRP.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-35141-9en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue8en
dc.identifier.orcidMunson, Jennifer [0000-0002-9477-1505]en
dc.identifier.pmid30451884en
dc.identifier.urihttp://hdl.handle.net/10919/85870en
dc.identifier.volume2018en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshGlioblastomaen
dc.subject.meshBrain Neoplasmsen
dc.subject.meshNeoplasm Invasivenessen
dc.subject.meshDisease Models, Animalen
dc.subject.meshReceptors, CXCR4en
dc.subject.meshChemokine CXCL12en
dc.titleConvective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine modelen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dcterms.dateAccepted2018-10-26en

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Scholarly Works, Biomedical Engineering and Mechanics
Destination Area: Adaptive Brain and Behavior (ABB)
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