Vasculogenic mimicry in small cell lung cancer

Stuart C Williamson; Robert L Metcalf; Francesca Trapani; Sumitra Mohan; Jenny Antonello; Benjamin Abbott; Hui Sun Leong; Christopher Chester; Nicole Simms; Radoslaw Polanski; Daisuke Nonaka; Lynsey Priest; Alberto Fusi; Fredrika Carlsson; Anders Carlsson; Mary J C Hendrix; Richard E B Seftor; Elisabeth A Seftor; Dominic G Rothwell; Andrew Hughes; James Hicks; Crispin Miller; Peter Kuhn; Gerard Brady; Kathryn L Simpson; Fiona H Blackhall; Caroline Dive

doi:10.1038/ncomms13322

Vasculogenic mimicry in small cell lung cancer

Stuart C Williamson, Robert L Metcalf, Francesca Trapani, Sumitra Mohan, Jenny Antonello, Benjamin Abbott, Hui Sun Leong, Christopher Chester, Nicole Simms, Radoslaw Polanski, Daisuke Nonaka, Lynsey Priest, Alberto Fusi, Fredrika Carlsson, Anders Carlsson, Mary J C Hendrix, Richard E B Seftor, Elisabeth A Seftor, Dominic G Rothwell, Andrew HughesJames Hicks, Crispin Miller, Peter Kuhn, Gerard Brady, Kathryn L Simpson, Fiona H Blackhall, Caroline Dive

Research output: Contribution to journal › Article › peer-review

Abstract

Small 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.

Original language	English
Pages (from-to)	13322
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13322 https://doi.org/10.1038/ncomms13322
Publication status	Published - 9 Nov 2016

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Williamson, S. C., Metcalf, R. L., Trapani, F., Mohan, S., Antonello, J., Abbott, B., Leong, H. S., Chester, C., Simms, N., Polanski, R., Nonaka, D., Priest, L., Fusi, A., Carlsson, F., Carlsson, A., Hendrix, M. J. C., Seftor, R. E. B., Seftor, E. A., Rothwell, D. G., ... Dive, C. (2016). Vasculogenic mimicry in small cell lung cancer. Nature Communications, 7, 13322. https://doi.org/10.1038/ncomms13322, https://doi.org/10.1038/ncomms13322

@article{2013936678754d4482d2e22418519952,

title = "Vasculogenic mimicry in small cell lung cancer",

abstract = "Small 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.",

author = "Williamson, {Stuart C} and Metcalf, {Robert L} and Francesca Trapani and Sumitra Mohan and Jenny Antonello and Benjamin Abbott and Leong, {Hui Sun} and Christopher Chester and Nicole Simms and Radoslaw Polanski and Daisuke Nonaka and Lynsey Priest and Alberto Fusi and Fredrika Carlsson and Anders Carlsson and Hendrix, {Mary J C} and Seftor, {Richard E B} and Seftor, {Elisabeth A} and Rothwell, {Dominic G} and Andrew Hughes and James Hicks and Crispin Miller and Peter Kuhn and Gerard Brady and Simpson, {Kathryn L} and Blackhall, {Fiona H} and Caroline Dive",

year = "2016",

month = nov,

day = "9",

doi = "10.1038/ncomms13322",

language = "English",

volume = "7",

pages = "13322",

journal = "Nature Communications",

issn = "2041-1723",

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Williamson, SC, Metcalf, RL, Trapani, F, Mohan, S, Antonello, J, Abbott, B, Leong, HS, Chester, C, Simms, N, Polanski, R, Nonaka, D, Priest, L, Fusi, A, Carlsson, F, Carlsson, A, Hendrix, MJC, Seftor, REB, Seftor, EA, Rothwell, DG, Hughes, A, Hicks, J, Miller, C, Kuhn, P, Brady, G, Simpson, KL, Blackhall, FH & Dive, C 2016, 'Vasculogenic mimicry in small cell lung cancer', Nature Communications, vol. 7, pp. 13322. https://doi.org/10.1038/ncomms13322, https://doi.org/10.1038/ncomms13322

TY - JOUR

T1 - Vasculogenic mimicry in small cell lung cancer

AU - Williamson, Stuart C

AU - Metcalf, Robert L

AU - Trapani, Francesca

AU - Mohan, Sumitra

AU - Antonello, Jenny

AU - Abbott, Benjamin

AU - Leong, Hui Sun

AU - Chester, Christopher

AU - Simms, Nicole

AU - Polanski, Radoslaw

AU - Nonaka, Daisuke

AU - Priest, Lynsey

AU - Fusi, Alberto

AU - Carlsson, Fredrika

AU - Carlsson, Anders

AU - Hendrix, Mary J C

AU - Seftor, Richard E B

AU - Seftor, Elisabeth A

AU - Rothwell, Dominic G

AU - Hughes, Andrew

AU - Hicks, James

AU - Miller, Crispin

AU - Kuhn, Peter

AU - Brady, Gerard

AU - Simpson, Kathryn L

AU - Blackhall, Fiona H

AU - Dive, Caroline

PY - 2016/11/9

Y1 - 2016/11/9

N2 - Small 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.

AB - Small 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.

UR - https://europepmc.org/articles/PMC5105195

U2 - 10.1038/ncomms13322

DO - 10.1038/ncomms13322

M3 - Article

C2 - 27827359

SN - 2041-1723

VL - 7

SP - 13322

JO - Nature Communications

JF - Nature Communications

ER -

Vasculogenic mimicry in small cell lung cancer

Abstract

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