dc.contributor.author | Dunleavey, James M. | en_US |
dc.contributor.author | Xiao, Lin | en_US |
dc.contributor.author | Thompson, Joshua | en_US |
dc.contributor.author | Kim, Mi Mi | en_US |
dc.contributor.author | Shields, Janiel M. | en_US |
dc.contributor.author | Shelton, Sarah E. | en_US |
dc.contributor.author | Irvin, David M. | en_US |
dc.contributor.author | Brings, Victoria E. | en_US |
dc.contributor.author | Ollila, David | en_US |
dc.contributor.author | Brekken, Rolf A. | en_US |
dc.contributor.author | Dayton, Paul A. | en_US |
dc.contributor.author | Melero-Martin, Juan M. | en_US |
dc.contributor.author | Dudley, Andrew C. | en_US |
dc.date.accessioned | 2015-05-04T15:27:32Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.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. http://dx.doi.org/10.1038/ncomms6200. | en |
dc.identifier.issn | 2041-1723 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034952 | |
dc.description.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. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/ncomms6200 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261234/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Vasculogenic mimicry | en |
dc.subject | tumor angiogenesis | en |
dc.subject | tumor endothelial cells | en |
dc.subject | melanoma | en |
dc.subject | tumor microenvironment | en |
dc.subject | tumor heterogeneity | en |
dc.subject | anti-angiogenic therapy | en |
dc.title | Vascular channels formed by subpopulations of PECAM1+ melanoma cells | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature communications | en |
dash.depositing.author | Melero-Martin, Juan M. | en_US |
dc.date.available | 2015-05-04T15:27:32Z | |
dc.identifier.doi | 10.1038/ncomms6200 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Melero-Martin, Juan | |