The procoagulant state of the VX-2 tumor in rabbit lung in vivo--relative accumulation of fibrinogen, prothrombin, plasminogen, antithrombin and heparin cofactor II within the tumor.
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-alpha, 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-alpha, 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.
Hatton
M W
MW
Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada. hattonm@mcmaster.ca
Ross
B
B
Bardossy
L
L
Southward
S M
SM
DeReske
M
M
Richardson
M
M
Blajchman
M A
MA
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis; D015844:Heparin Cofactor II / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood* / Q000098:blood supply; D009374:Neoplasms, Experimental / Q000097:blood* / Q000098:blood supply; D009389:Neovascularization, Pathologic; D010958:Plasminogen / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011817:Rabbits
D000991:Antithrombins; D015844:Heparin Cofactor II; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen