Specific accumulation oftumor-derived adhesion factor intumor bloodvessels andincapillary tube-like structures ofcultured vascular endothelial cells

Tumor-derived adhesion factor (TAF)was previously identified asacell adhesion molecule secreted by humanbladder carcinoma cell lineEJ-1. Toelucidate the physiological function ofTAF,weexamined itsdistribution in humannormal andtumortissues. Immunochemical staining withananti-TAF monoclonal antibody showed that TAFwas specifically accumulated insmall blood vessels andcapillaries within andadjacent totumornests, butnotinthose innormal tissues. Tumorbloodvessel-specific staining ofTAFwas observed invarious humancancers, suchasesophagus, brain, lung, andstomach cancers. Double immunofluorescent stain- ingshowedapparent colocalization ofTAF andtypeIV collagen inthevascular basement membrane. Invitro exper- iments demonstrated that TAFpreferentially boundtotype IV collagen amongvarious extracellular matrix components tested. Incell culture experiments, TAFpromoted adhesion of humanumbilical veinendothelial cells totypeIVcollagen substrate andinduced their morphological change. Further- more, whentheendothelial cells wereinduced toformcapillary tube-like structures bytype Icollagen, TAFandtype IVcollagen wereexclusively detected onthetubular structures. Thecapillary tubeformation invitro wasprevented byheparin, which inhibited thebinding ofTAFtotheendothelial cells. These results strongly suggest that TAFcontributes totheorganization ofnewcapillary vessels intumortissues bymodulating theinteraction ofendo- thelial cells withtype IVcollagen. Angiogenesis, orneovascularization, iscritical fornormal