Vasculogenic mimicry in small cell lung cancer

Williamson, S. C. et al. (2016) Vasculogenic mimicry in small cell lung cancer. Nature Communications, 7, 13322. (doi: 10.1038/ncomms13322) (PMID:27827359) (PMCID:PMC5105195)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Professor Crispin
• Authors: Williamson, S. C., Metcalf, R. L., Trapani, F., Mohan, S., Antonello, J., Abbott, B., Leong, H. S., Chester, C. P. E., 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., Hughes, A., Hicks, J., Miller, C., Kuhn, P., Brady, G., Simpson, K. L., Blackhall, F. H., and Dive, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright r The Author(s) 2016
• First Published: First published in Nature Communications 7:13322
• Publisher Policy: Reproduced under a Creative Commons Licence