@article{3f05b191d58542009840a8c48ed2b6b0,
title = "Vascular channels formed by subpopulations of PECAM1 + melanoma cells",
abstract = "Targeting the vasculature remains a promising approach for treating solid tumours; however, the mechanisms of tumour neovascularization are diverse and complex. Here we uncover a new subpopulation of melanoma cells that express the vascular cell adhesion molecule PECAM1, but not VEGFR-2, and participate in a PECAM1-dependent form of vasculogenic mimicry (VM). Clonally derived PECAM1 + tumour cells coalesce to form PECAM1-dependent networks in vitro and they generate well-perfused, vascular endothelial growth factor (VEGF)-independent channels in mice. The neural crest specifier AP-2α is diminished in PECAM1 + melanoma cells and is a transcriptional repressor of PECAM1. Re-introduction of AP-2α into PECAM1 + tumour cells represses PECAM1 and abolishes tube-forming ability, whereas AP-2α knockdown in PECAM1' tumour cells upregulates PECAM1 expression and promotes tube formation. Thus, VM-competent subpopulations, rather than all cells within a tumour, may instigate VM, supplant host-derived endothelium, and form PECAM1-dependent conduits that are not diminished by neutralizing VEGF.",
author = "Dunleavey, {James M.} and Lin Xiao and Joshua Thompson and Kim, {Mi Mi} and Shields, {Janiel M.} and Shelton, {Sarah E.} and Irvin, {David M.} and Brings, {Victoria E.} and Ollila, {David W.} and Brekken, {Rolf A.} and Dayton, {Paul A.} and Melero-Martin, {Juan M.} and Dudley, {Andrew C.}",
note = "Funding Information: A.C.D. is supported by grants from the National Institutes of Health (R00-CA140708 and R01-CA177875) and the University Cancer Research Fund at UNC Chapel Hill. J.M.D. is supported by a pre-doctoral fellowship (F31-CA174245) from the National Institutes of Health. P.A.D. is supported by the National Institutes of Health (R01-CA170665). We acknowledge NIH grant S10-OD010410 for the shared ultrasound instrumentation. We thank Kirk McNaughton and Ashley Ezzell in the Cell Biology and Physiology Histology Research Core and the UNC Microscopy Services Laboratory in the UNC Department of Pathology and Laboratory Medicine. We thank Drs William Kim and James Bear at UNC Chapel Hill for sharing the mouse melanoma lines from DBraf/ Pten−/− mice. Finally, we thank Dr Eleni Tzima at UNC Chapel Hill for sharing the Pecam1 KO mice. Funding Information: A.C.D. is supported by grants from the National Institutes of Health (R00-CA140708 and R01-CA177875) and the University Cancer Research Fund at UNC Chapel Hill. J.M.D. is supported by a pre-doctoral fellowship (F31-CA174245) from the National Institutes of Health. P.A.D. is supported by the National Institutes of Health (R01-CA170665). We acknowledge NIH grant S10-OD010410 for the shared ultrasound instrumentation. We thank Kirk McNaughton and Ashley Ezzell in the Cell Biology and Physiology Histology Research Core and the UNC Microscopy Services Laboratory in the UNC Department of Pathology and Laboratory Medicine. We thank Drs William Kim and James Bear at UNC Chapel Hill for sharing the mouse melanoma lines from DBraf/ Pten / mice. Finally, we thank Dr Eleni Tzima at UNC Chapel Hill for sharing the Pecam1 KO mice.",
year = "2014",
month = oct,
day = "22",
doi = "10.1038/ncomms6200",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}