Vascular channels formed by subpopulations of PECAM1+ melanoma cells

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Vascular channels formed by subpopulations of PECAM1+ melanoma cells

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Title: Vascular channels formed by subpopulations of PECAM1+ melanoma cells
Author: Dunleavey, James M.; Xiao, Lin; Thompson, Joshua; Kim, Mi Mi; Shields, Janiel M.; Shelton, Sarah E.; Irvin, David M.; Brings, Victoria E.; Ollila, David; Brekken, Rolf A.; Dayton, Paul A.; Melero-Martin, Juan M.; Dudley, Andrew C.

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Citation: Dunleavey, J. M., L. Xiao, J. Thompson, M. M. Kim, J. M. Shields, S. E. Shelton, D. M. Irvin, et al. 2014. “Vascular channels formed by subpopulations of PECAM1+ melanoma cells.” Nature communications 5 (1): 5200. doi:10.1038/ncomms6200.
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Abstract: Targeting the vasculature remains a promising approach for treating solid tumors; however, the mechanisms of tumor 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+ tumor cells coalesce to form PECAM1-dependent networks in vitro and they generate well-perfused, VEGF-independent channels in mice. The neural crest specifier AP-2α is diminished in PECAM1+ melanoma cells and is a transcriptional repressor of PECAM1. Reintroduction of AP-2α into PECAM1+ tumor cells represses PECAM1 and abolishes tube-forming ability whereas AP-2α knockdown in PECAM1− tumor cells up-regulates PECAM1 expression and promotes tube formation. Thus, VM-competent subpopulations, rather than all cells within a tumor, may instigate VM, supplant host-derived endothelium, and form PECAM1-dependent conduits that are not diminished by neutralizing VEGF.
Published Version: doi:10.1038/ncomms6200
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