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dc.contributor.authorWilliamson, Stuart
dc.contributor.authorMetcalf, Robert
dc.contributor.authorTrapani, Francesca
dc.contributor.authorMohan, Sumitra
dc.contributor.authorAntonello, Jenny
dc.contributor.authorAbbott, Benjamin
dc.contributor.authorLeong, Hui Sun
dc.contributor.authorChester, Christopher P E
dc.contributor.authorSimms, Nicole
dc.contributor.authorPolanski, Radoslaw
dc.contributor.authorNonaka, Daisuke
dc.contributor.authorPriest, Lynsey
dc.contributor.authorFusi, Alberto
dc.contributor.authorCarlsson, F
dc.contributor.authorCarlsson, A
dc.contributor.authorHendrix, M
dc.contributor.authorSeftor, R
dc.contributor.authorSeftor, E
dc.contributor.authorRothwell, Dominic G
dc.contributor.authorHughes, Andrew
dc.contributor.authorHicks, J
dc.contributor.authorMiller, Crispin J
dc.contributor.authorKuhn, Peter
dc.contributor.authorBrady, Ged
dc.contributor.authorSimpson, Kathryn L
dc.contributor.authorBlackhall, Fiona H
dc.contributor.authorDive, Caroline
dc.date.accessioned2016-12-09T19:27:01Z
dc.date.available2016-12-09T19:27:01Z
dc.date.issued2016-11-09
dc.identifier.citationVasculogenic mimicry in small cell lung cancer. 2016, 7:13322 Nat Communen
dc.identifier.issn2041-1723
dc.identifier.pmid27827359
dc.identifier.doi10.1038/ncomms13322
dc.identifier.urihttp://hdl.handle.net/10541/620033
dc.description.abstractSmall cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.
dc.language.isoenen
dc.rightsArchived with thanks to Nature communicationsen
dc.titleVasculogenic mimicry in small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentClinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, Manchester M20 4BX, UKen
dc.identifier.journalNature Communicationsen
refterms.dateFOA2018-12-17T14:45:41Z
html.description.abstractSmall cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.


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