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

SUBMITTER: Dunleavey JM 

PROVIDER: S-EPMC4261234 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature