Fibrin monomer increases platelet adherence to tumor cells in a flowing system: A possible role in metastasis?

Considerable evidence exists linking hemostasis and malignancy. Platelet ad hesion to tumor cells has been implicated in the metastatic process. Plasma fibrinogen (Fg) and fibrin (Fn) monomer, increased in cancer, may play a r ole in tumor biology. Binding of Fn monomer to tumor cells and its effect o n platelet-tumor cell adhesion in a flowing system were studied. Fn monomer was produced by adding thrombin (1 mu/mL) to FXIII- and plasminogen-free F g in the presence of Gly-Pro-Arg-Pro (GPRP) amide. Fn monomer binding to li ve A375 cells was visualized by confocal laser scanning microscopy (CLSM). Adherent cells were perfused for Ih with Fn monomer, washed and stained in situ with anti-human Fn (American Biogenetic Sciences, Inc.) followed by go at anti-mouse IgG(FITC). Platelet adherence to Fn monomer treated A375 cell s was performed under flow conditions by passing platelets (5x10(4)/mu l; 0 .25 mL/min; labeled with the carbocyanine dye DiI) over the tumor cells for 30 min. CLSM images were obtained after washing. There was considerable bi nding of Fn monomer, but not Fg alone. Platelets adhered relatively weakly to untreated A375 cells and this was not significantly affected by pre-trea tment of the tumor cells with fibrinogen or thrombin. However, pre-treatmen t with Fn monomer resulted in extensive platelet binding to tumor cells, su ggesting that coagulation activation and the subsequent increase in circula ting Fn monomer may enhance platelet adhesion to circulating tumor cells an d thereby facilitate metastatic spread. (C) 1998 Elsevier Science Ltd.