von Willebrand factor interacts with malignant hematopoietic cell lines: evidence for the presence of specific binding sites and modification of von Willebrand factor structure and function.
von Willebrand factor (vWf) mediates the adherence of platelets to exposed vascular subendothelium. During hematogenous metastasis in certain model systems, platelets are also deposited at endothelial surfaces in heterotypic aggregates with tumor cells. The role of vWf in this metastatic event was investigated by examining the interaction between purified iodine 125-labeled vWf and the human tumor cell lines, U937 and CA46. vWf-tumor cell binding was specific, partially reversible, and saturable at 4 degrees C. At 37 degrees C, however, U937 cell binding sites could not be saturated, suggesting endocytosis as a possible mechanism of interaction. When constant amounts of vWf were added, interactions with tumor cells were complete after 60 minutes, but rapidly dissociated over the next 2 hours. With the addition of specific proteinase inhibitors, vWf remained in stable association with tumor cells throughout a 3-hour time course. Loss of vWf antigen in supernatant samples complemented the 125I-labeled vWf bound directly to tumor cells. However, disproportionately large reductions in vWf functional activity were observed and correlated with alterations in multimeric structure. These data suggest an initial binding of vWf to some tumor cells, followed by a time-dependent loss of structural and functional integrity. VWf may contribute to tumor cell arrest within the microvasculature and may influence other tumor cell-subendothelial interactions as the adhesive function of vWf is subsequently modified.
Floyd
C M
CM
Division of Hematology/Oncology, George Washington University Medical Center, Washington, D.C. 20037.
Irani
K
K
Kind
P D
PD
Kessler
C M
CM
D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
D009842:Oligopeptides; D014841:von Willebrand Factor; C046617:arginyl-glycyl-aspartyl-serine