Endothelial-like cells derived directly from human tumor xenografts

Tumor-associated endothelial cells (TAECs) harboring various genomic abnormalities have been described in human cancers although their origins remain obscure. We generated 4 human cancer cell lines tagged with multiple markers, grew them as xenografts, and characterized their TAECs. Depending on their tumor of origin, 5-40% of TAECs reproducibly expressed all tags. Tagged TAECs (tTAECS) were morphologically, immunologically and functionally similar, although not identical, to normal endothelial cells (ECs) and contained only human chromosomes. tTAECs underwent a senescent-like proliferative arrest after several in vitro passages, but could be immortalized by telomerase, thus allowing us to show that the retention of the EC phenotype was of long-term duration. In contrast, nonimmortalized tTAECs could be propagated in vivo where they incorporated into the tumor neo-vasculature. Although consistent with previous reports that some tumor cells may undergo vasculogenic mimicry (VM), the tumor-derived endothelial-like cells described here appear distinctly different. Moreover, their properties and behaviors are more durable than expected for cells undergoing VM, are not the result of fusions between ECs and tumor cells, and are cell autonomous. These findings could have significant implications for therapies that target tumor angiogenesis.