Summary
During their growth, many malignant solid tumors elicit a hemostatic response in the
host. In this report, the fluxes of various rabbit plasma hemostatic proteins into
pulmonary VX-2 tumors have been measured in vivo. VX-2 cells were contained within
a small rabbit plasma clot which was injected intravenously into rabbits. At 28 d,
each rabbit was injected intravenously with two radiolabeled (131I, 125I) proteins selected from fibrinogen, prothrombin, antithrombin-α, heparin cofactor
II, or plasminogen-I or -II. After allowing the labeled proteins to circulate for
10-200 min, each rabbit was perfused with Krebs-Henseleit solution and the lungs excised.
Solid tumors 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 exsanguination for each
protein at each time interval. Maximum flux rates were calculated (as pmol/g of tumor/min):
Fibrinogen, 65.0; prothrombin, 53.0; antithrombin-α, 24.1; HCII, 17.2; plasminogen-II,
5.0; and plasminogen-I, 3.2. Using immunocytochemical staining, fibrin(ogen) was distributed
heterogeneously within the VX-2 tumor, appearing largely in the perinodular region
and in the necrotic core. From the net fluxes of these proteins, the profile of chronic
hemostasis associated with the VX-2 tumor was shown to differ markedly from the hemostatic
response that occurs after an acute vascular injury.
Keywords
Tumor - procoagulant state - hemostasis factors - fibrinogen
