Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry

We recently have introduced the term vasculogenic mimicry to describe the u nique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryo nic vasculogenic networks formed by differentiating endothelial cells. In t he current study, we address the biological significance of several endothe lial-associated molecules (revealed by microarray analysis) with respect to expression and function in highly aggressive and poorly aggressive human c utaneous melanoma cell lines (established from the same patient). In a comp arative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with 1g and epidermal growth factor homolog y domains-1) was strongly expressed in the highly aggressive tumor cells wi th a low level of expression in one of the poorly aggressive cell lines. Va scular endothelial (VE)-cadherin was exclusively expressed by highly aggres sive melanoma cells and was undetectable in the poorly aggressive tumor cel ls, suggesting the possibility of a vasculogenic switch. Down-regulation of VE-cadherin expression in the aggressive melanoma cells abrogated their ab ility to form vasculogenic networks and directly tested the hypothesis that VE-cadherin is critical in melanoma vasculogenic mimicry. These results hi ghlight the plasticity of aggressive melanoma cells and call into question their possible genetic reversion to an embryonic phenotype, This finding co uld pose a significant clinical challenge in targeting tumor cells that may masquerade as circulating endothelial cells or other embryonic-like stem c ells.