Figure 8.

Endogenous cancer-derived MPs accelerate thrombus formation in a P-selectin–dependent manner. (A) 2 × 10⁵ Panc02 cells overexpressing GFP were injected subcutaneously into the right flank of a mouse. 5 wk later, chemical injury of the mesentery was induced, and fluorescence was detected in the absence (left, Control) or presence of circulating P-selectin blocking antibody (right, P-selectin antibody; n = 6 thrombi in three mice). (B–D). Kinetics of thrombosis in wild-type mice, wild-type mice infused with Panc02 MPs (WT+MPs, 0.2 µg of MP-associated proteins/g/mouse), or with Panc02 MPs plus 2 µg/g/mouse of anti P-selectin blocking antibody (WT+MPs+anti P-sel). Controls were performed by infusion of anti–P-selectin antibody into wild-type mice (WT+anti P-sel) or by infusing an irrelevant antibody into wild-type mice perfused with MPs (WT+MPs+Irr Ab). Injury of the mesenteric vessels was chemically induced, and the time to vessel occlusion for arterioles (n = 10 for WT, n = 7 for WT+anti Psel, n = 10 for WT+MPs, n = 7 for WT+MPs+anti Psel, and n = 8 for WT+MPs+Irr Ab; B) and veinules (n = 13 for WT, n = 7 for WT+anti Psel, n = 7 for WT+MPs, n = 7 for WT+MPs+anti Psel, and n = 8 for WT+MPs+Irr Ab; C) was measured. (D) Bleeding times were determined for all conditions studied (n = 13 for WT, n = 7 for WT+anti Psel, n = 8 for WT+MPs, n = 6 for WT+MPs+Anti Psel, and n = 8 for WT+MPs+Irr Ab). One thrombus was performed per mouse. Horizontal bars designate median values. Experiments were independently performed three times (A) and at least seven times (B–D). **, P < 0.01; *, P < 0.05.