thromboplastin and Neoplasm-Seeding

A correlation between cancer and hypercoagulability has been described for more than a century. Patients with cancer are at increased risk for thrombotic complications and the clotting initiator protein, tissue factor (TF), is possibly involved in this process. Moreover, TF may promote angiogenesis and tumor growth. In addition to TF, thrombin seems to play a relevant role in tumor biology, mainly through activation of protease-activated receptor-1 (PAR-1). In the present study, we prospectively studied 39 lung adenocarcinoma patients in relation to the tumor expression levels of TF and PAR-1 and their correlation with thrombosis outcome and survival. Immunohistochemical analysis showed TF positivity in 22 patients (56%), most of them in advanced stages (III and IV). Expression of PAR-1 was found in 15 patients (39%), most of them also in advanced stages (III and IV). Remarkably, no correlation was observed between the expression of TF or PAR-1 and risk for thrombosis development. On the other hand, patients who were positive for TF or PAR-1 tended to have decreased long-term survival. We conclude that immunolocalization of either TF or PAR-1 in lung adenocarcinoma may predict a poor prognosis although lacking correlation with thrombosis outcome.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Neoplasm Seeding; Prognosis; Prospective Studies; Receptor, PAR-1; Thromboplastin; Thrombosis

Peri-tumour fibrin is a consistent feature of tumour stroma and is deposited shortly after tumour cell inoculation. Since there are several ways in which fibrin may be beneficial to tumour growth, it is possible that the ability of normal or malignant tissue to generate fibrin may influence metastasis. Many normal tissues and tumour cells possess a procoagulant activity that is due to a complex of tissue factor and factor VII. We have measured this tissue procoagulant activity in normal rats, rats stabilised on Warfarin and similarly anticoagulated animals injected with factor VII. The effect of Warfarin and factor VII administration on pulmonary seeding following injection of MC28 fibrosarcoma cells was also assessed. Procoagulant activity in adrenal, lung and colon was significantly reduced by Warfarin (P less than 0.001). Administration of factor VII significantly increased lung and adrenal tissue procoagulant activity in anticoagulated rats (P less than 0.02). Warfarinised rats had significantly slower primary tumour growth (P less than 0.001) and fewer lung deposits than control animals (P less than 0.001). Injection of factor VII restored pulmonary seeding to control levels (P less than 0.001). Warfarin did not affect the ability of the cells to adhere in vitro and did not reduce the number of tumour cells physically trapped in the lungs after intravenous injection. It is concluded that the procoagulant activity of normal tissues may influence their ability to support tumour growth and that the antimetastatic effect of Warfarin may be at least partly due to a reduction in the availability of the factor VII required for this activity.

Topics: Adrenal Glands; Animals; Cell Adhesion; Colon; Factor VII; Factor X; Fibrosarcoma; Liver; Lung; Lung Neoplasms; Neoplasm Seeding; Neoplasms, Experimental; Rats; Thromboplastin; Warfarin

Topics: Breast Neoplasms; Female; Humans; Lung Neoplasms; Middle Aged; Necrosis; Neoplasm Metastasis; Neoplasm Seeding; Neoplasms, Radiation-Induced; Radiotherapy; Skin Neoplasms; Thromboplastin