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
Mwc. Hatton et al., 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, THROMB HAEM, 82(6), 1999, pp. 1694-1702
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.