TEM8 interacts with the cleaved C5 domain of collagen α3(VI)

Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha3(VI) was mapped to its COOH-terminal C5 domain. Remarkably, collagen alpha3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8. These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis.