Tumor-derived adhesion factor (TAF) was previously identified as a
cell adhesion molecule secreted by human bladder
carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and
tumor tissues. Immunochemical staining with an anti-TAF
monoclonal antibody showed that TAF was specifically accumulated in small blood vessels and capillaries within and adjacent to
tumor nests, but not in those in normal tissues.
Tumor blood vessel-specific staining of TAF was observed in various human
cancers, such as esophagus, brain, lung, and
stomach cancers. Double immunofluorescent staining showed apparent colocalization of TAF and
type IV collagen in the vascular basement membrane. In vitro experiments demonstrated that TAF preferentially bound to
type IV collagen among various extracellular matrix components tested. In cell culture experiments, TAF promoted adhesion of human umbilical vein endothelial cells to
type IV collagen substrate and induced their morphological change. Furthermore, when the endothelial cells were induced to form capillary tube-like structures by
type I collagen, TAF and
type IV collagen were exclusively detected on the tubular structures. The capillary tube formation in vitro was prevented by
heparin, which inhibited the binding of TAF to the endothelial cells. These results strongly suggest that TAF contributes to the organization of new capillary vessels in
tumor tissues by modulating the interaction of endothelial cells with
type IV collagen.