Karpatkin S, Pearlstein E, Ambrogio C, Coller B S
Department of Medicine, New York University Medical Center, New York 10016.
J Clin Invest. 1988 Apr;81(4):1012-9. doi: 10.1172/JCI113411.
Platelet-adhesive protein-tumor cell interaction was studied in vitro and in vivo. Monoclonal antibody 10E5, which inhibits binding of fibronectin and von Willebrand factor to the platelet membrane glycoprotein GPIIb-GPIIIa complex, inhibited the binding of mouse CT26 and human HCT8 colon carcinoma cells to platelets by 63-65%, whereas an irrelevant monoclonal antibody, 3B2, had no effect. Monoclonal antibody 6D1, which inhibits binding of von Willebrand factor to GPIb, also had no effect. RGDS, a tetrapeptide that represents the adhesive domain of fibronectin and von Willebrand factor inhibited binding of the tumors to platelets by 64-69%. Monospecific polyclonal antifibronectin antibody inhibited binding by 60-82%; anti-von Willebrand factor antibody inhibited binding by 75-81%. In vivo, polyclonal monospecific anti-mouse von Willebrand factor antibody inhibited pulmonary metastases induced by CT26 tumor cells by 53-64%, B16a amelanotic melanoma cells by 45% and T241 Lewis bladder cells by 46% without induction of thrombocytopenia. Pulmonary metastases with CT26 cells could be inhibited by induction of thrombocytopenia, and reconstituted by infusion of either murine or human platelets. Reconstitution of pulmonary metastases with human platelets could be inhibited 77% by preincubation of human platelets with monoclonal antibody 10E5 before infusion of platelets into mice. Thus, platelets appear to contribute to metastases by their adhesive interaction with tumor cells via the adhesive proteins fibronectin and von Willebrand factor.
在体外和体内研究了血小板粘附蛋白与肿瘤细胞的相互作用。单克隆抗体10E5可抑制纤连蛋白和血管性血友病因子与血小板膜糖蛋白GPIIb - GPIIIa复合物的结合，它可使小鼠CT26和人HCT8结肠癌细胞与血小板的结合减少63% - 65%，而无关的单克隆抗体3B2则无此作用。单克隆抗体6D1可抑制血管性血友病因子与GPIb的结合，也无作用。RGDS是一种代表纤连蛋白和血管性血友病因子粘附结构域的四肽，可使肿瘤与血小板的结合减少64% - 69%。单特异性多克隆抗纤连蛋白抗体可使结合减少60% - 82%；抗血管性血友病因子抗体可使结合减少75% - 81%。在体内，单特异性多克隆抗小鼠血管性血友病因子抗体可使CT26肿瘤细胞诱导的肺转移减少53% - 64%，使B16a无黑色素黑色素瘤细胞诱导的肺转移减少45%，使T241刘易斯膀胱癌细胞诱导的肺转移减少46%，且不会引起血小板减少。CT26细胞引起的肺转移可通过诱导血小板减少来抑制，并可通过输注鼠或人血小板来重建。在将人血小板输注到小鼠体内之前，用人血小板与单克隆抗体10E5预孵育，可使用人血小板重建的肺转移减少77%。因此，血小板似乎通过其与肿瘤细胞经由粘附蛋白纤连蛋白和血管性血友病因子的粘附相互作用而促进转移。
