Endothelium and Cancer: Basic and Clinical Aspects

Thromboembolic complications as well as laboratory abnormalities in hemostatic parameters are frequently observed in cancer patients. Tissue factor (TF) has been documented to play a crucial role in the pathophysiology of thrombosis and, among other coagulation proteins, in tumor growth and metastatic spread. The principal inhibitor of TF-dependent pathway of blood coagulation is tissue factor pathway inhibitor (TFPI). Its presence in cancer tissue was not detected in previous studies. There exists a second inhibitor of tissue factor dependent pathway, TFPI-2, also known as placental protein (PP5) or matrix-associated serine protease inhibitor (MSPI). TFPI-2/ PP5 inhibits the amidolytic and proteolytic activity of TF/VIIa complex. TFPI-2/PP5 is a strong inhibitor of human factor XIa amidolytic activity, human plasma kallikrein, plasmin, trypsin and chymotrypsin. TFPI-2/PP5, synthesized predominantly by the endothelial cells of small blood vessels, is secreted primarily (60–90%) into the extravascular matrix. However, information on the presence TFPI-2 at the tumor burden still remains obscure. The purpose of this study was to evaluate the expression of the TFPI-2 in situ in several human neoplasms. The study employed immunohistochemical procedures. TFPI-2 expression was observed in neoplastic cells of laryngeal, breast, gastric, colon, pancreatic, renal, endometrial cancer and non-small cell lung cancer (NSCLC), as well as glial neoplasms. The intensity of staining was inconsistent. Higher intensity of staining for TFPI-2 was detected in more differentiated tumors. Breast, gastric, endometrial and colon cancer cells revealed populations of cells that were either TFPI-2 positive or negative. Antigenic TFPI-2 was also demonstrated in tumor infiltrating macrophages in the case of NSCLC, gastric and renal cancers. In gastric cancer a staining for TFPI-2 in tumor stroma was revealed. TFPI-2 was also observed in normal tissue of the larynx, breast, stomach, colon, pancreas, kidney, lung and endometrium. The data demonstrate that the expression of TFPI-2 diminishes with an increasing degree of malignancy, which may suggest a role for TFPI-2 in the maintenance of tumor stability and inhibition of the growth of neoplasms. P 02 Up-Regulation of Cyclin D1 in Cultured Human Endothelial Cells in Response to Exogenous Tissue Factor A. Pradier1, N.J. James2, C. Ettelaie1 1University of Hull, Hull, 2Leeds University, Leeds, UK