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dc.contributor.authorLi, J
dc.contributor.authorZormpas-Petridis, K
dc.contributor.authorBoult, JKR
dc.contributor.authorReeves, EL
dc.contributor.authorHeindl, A
dc.contributor.authorVinci, M
dc.contributor.authorLopes, F
dc.contributor.authorCummings, C
dc.contributor.authorSpringer, CJ
dc.contributor.authorChesler, L
dc.contributor.authorJones, C
dc.contributor.authorBamber, JC
dc.contributor.authorYuan, Y
dc.contributor.authorSinkus, R
dc.contributor.authorJamin, Y
dc.contributor.authorRobinson, SP
dc.date.accessioned2019-09-19T08:35:01Z
dc.date.issued2019-11
dc.identifier.citationCancer research, 2019, 79 (22), pp. 5874 - 5883
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3350
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-19-1595
dc.description.abstractIncreased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic resonance (MR) elastography can noninvasively and quantitatively map the viscoelastic properties of tumors in vivo and thus has clear clinical applications. Herein, we used MR elastography, coupled with computational histopathology, to interrogate the contribution of collagen to the tumor biomechanical phenotype and to evaluate its sensitivity to collagenase-induced stromal modulation. Elasticity ( G d ) and viscosity ( G l ) were significantly greater for orthotopic BT-474 ( G d = 5.9 ± 0.2 kPa, G l = 4.7 ± 0.2 kPa, n = 7) and luc-MDA-MB-231-LM2-4 ( G d = 7.9 ± 0.4 kPa, G l = 6.0 ± 0.2 kPa, n = 6) breast cancer xenografts, and luc-PANC1 ( G d = 6.9 ± 0.3 kPa, G l = 6.2 ± 0.2 kPa, n = 7) pancreatic cancer xenografts, compared with tumors associated with the nervous system, including GTML/ Trp53 KI/KI medulloblastoma ( G d = 3.5 ± 0.2 kPa, G l = 2.3 ± 0.2 kPa, n = 7), orthotopic luc-D-212-MG ( G d = 3.5 ± 0.2 kPa, G l = 2.3 ± 0.2 kPa, n = 7), luc-RG2 ( G d = 3.5 ± 0.2 kPa, G l = 2.3 ± 0.2 kPa, n = 5), and luc-U-87-MG ( G d = 3.5 ± 0.2 kPa, G l = 2.3 ± 0.2 kPa, n = 8) glioblastoma xenografts, intracranially propagated luc-MDA-MB-231-LM2-4 ( G d = 3.7 ± 0.2 kPa, G l = 2.2 ± 0.1 kPa, n = 7) breast cancer xenografts, and Th- MYCN neuroblastomas ( G d = 3.5 ± 0.2 kPa, G l = 2.3 ± 0.2 kPa, n = 5). Positive correlations between both elasticity ( r = 0.72, P < 0.0001) and viscosity ( r = 0.78, P < 0.0001) were determined with collagen fraction, but not with cellular or vascular density. Treatment with collagenase significantly reduced G d ( P = 0.002) and G l ( P = 0.0006) in orthotopic breast tumors. Texture analysis of extracted images of picrosirius red staining revealed significant negative correlations of entropy with G d ( r = -0.69, P < 0.0001) and G l ( r = -0.76, P < 0.0001), and positive correlations of fractal dimension with G d ( r = 0.75, P < 0.0001) and G l ( r = 0.78, P < 0.0001). MR elastography can thus provide sensitive imaging biomarkers of tumor collagen deposition and its therapeutic modulation. SIGNIFICANCE: MR elastography enables noninvasive detection of tumor stiffness and will aid in the development of ECM-targeting therapies.
dc.formatPrint-Electronic
dc.format.extent5874 - 5883
dc.languageeng
dc.language.isoeng
dc.subjectCell Line, Tumor
dc.subjectExtracellular Matrix
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectCollagen
dc.subjectMagnetic Resonance Imaging
dc.subjectPhenotype
dc.subjectElasticity
dc.subjectFemale
dc.subjectElasticity Imaging Techniques
dc.titleInvestigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography.
dc.typeJournal Article
dcterms.dateAccepted2019-09-17
rioxxterms.versionofrecord10.1158/0008-5472.can-19-1595
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue22
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Computational Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Ultrasound & Optical Imaging
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Computational Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Ultrasound & Optical Imaging
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume79
pubs.embargo.terms12 months
icr.researchteamComputational Pathology & Integrated Genomicsen_US
icr.researchteamGlioma Teamen_US
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
icr.researchteamComputational Imagingen_US
icr.researchteamMagnetic Resonanceen_US
icr.researchteamPre-Clinical MRIen_US
icr.researchteamUltrasound & Optical Imagingen_US
dc.contributor.icrauthorZormpas Petridis, Konstantinosen
dc.contributor.icrauthorReeves, Emmaen
dc.contributor.icrauthorLi, Jinen
dc.contributor.icrauthorJamin, Yannen
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorChesler, Louisen
dc.contributor.icrauthorJones, Chrisen
dc.contributor.icrauthorBamber, Jeffreyen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorYuan, Yinyinen


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