The procoagulant state of the VX-2 tumor in rabbit lung in vivo - Relativeaccumulation of fibrinogen, prothrombin, plasminogen, antithrombin and heparin cofactor II within the tumor

During their growth, many malignant solid tumors elicit a hemostatic respon se in the host. In this report, the fluxes of various rabbit plasma hemosta tic proteins into pulmonary VX-2 tumors have been measured in vivo. VX-2 ce lls were contained within a small rabbit plasma clot which was injected int ravenously into rabbits. At 28 d, each rabbit was injected intravenously wi th two radiolabeled (I-131, I-125) proteins selected from fibrinogen, proth rombin, antithrombin-alpha, heparin cofactor II, or plasminogen-I or -II. A fter allowing the labeled proteins to circulate for 10-200 min, each rabbit was perfused with Krebs-HenseIeit solution and the lungs excised. Solid tu mors were isolated. weighed and measured for radioactivity content. A mean of 14 tumors/pair of lungs with a mean tumor weight of 0.3 g was obtained. Radioactivity per g of tumor was related to radioactivity/ml of blood at ex sanguination for each protein at each time interval. Maximum flux rates wer e calculated las pmol/g of tumor/min): Fibrinogen, 65.0; prothrombin, 53.0; antithrombin-alpha, 24.1; HCII, 17.2; plasminogen-II, 5.0; and plasminogen -I, 3.2. Using immunocytochemical staining, fibrin(ogen) was distributed he terogenously within the VX-2 tumor, appearing largely in the perimodular re gion and in the necrotic core. From the net fluxes of these proteins, the p rofile of chronic hemostasis associated with the VX-2 tumor was shown to di ffer markedly from the hemostatic response that occurs after an acute vascu lar injury.