Heterogeneous Expression of Protein C (PC), Protein S (PS) and Thrombomodulin (TM) in Human Colon Cancer Tissue.

Colon cancer is often complicated by thromboembolic episodes. It has been recognized that blood coagulation proteins play a role in malignant tumor progression and metastatic dissemination. An important inhibitory mechanism is provided by protein C (PC) system consisting of protein C, protein S (PS) and thrombomodulin (TM). Thrombin binds to membrane-bound TM and consequently activates PC. Active PC together with its cofactor - PS inactivates coagulation factors Va and VIIIa. Recently novel biological activities have been desribed for protein C system components that do not relate to its hemostatic functions. Active protein C exerts antiapoptotic activity towards endothelial cells (ECs) and activates proteolytic enzymes. It induces proliferation of ECs and angiogenesis. Protein S was documented to inhibit apoptosis as well as inflammatory and immunologic response.

The purpose of the study was to elucidate the solid phase interactions between colon cancer tissue and components of protein C system that may contribute to tumor progression. The tissues from colon cancer were obtained at surgical resection during radical treatment of 66 patients. The patients undergoing surgery have not received any previous anticancer therapy. Tumor fragments were processed acc. to AMeX method and than embedded in paraffin. Immunohistochemical studies (avidin-biotin complex-ABC - technique) were performed using polyclonal antibodies against PC, PS and TM.

Weak expression of PC was observed in cancer cells of two thirds of the examined specimens while in 4/66 cases there was no staining for PC in cancer cell bodies. One third of colon cancer fragments revealed strong expression of PC. Presence of PS was demonstrated in 64 cases of colon cancer, however its expression was irregular: a weak staining was observed in 60 cases and strong one - only in 4 cases. Two cases of colon cancer tissue have not revealed any staining for PS in cancer cells. Weak expression of TM was observed in two thirds of the examined cases, while a strong staining was revealed in one third of colon cancer tissues. However the expression of TM was inconsistent: not all cell bodies were TM-positive. The presence of PC and PS, but not TM was demonstrated in tumor associated macrophages. Furthermore, PS and TM antigens were localized in tumor stroma. Heterogeneous expression of PC system components in colon cancer tissue may indicate that their biological activity, exerted via their interplay with coagulation/fibrinolysis and regardless of their function in hemostasis, may modulate tumor growth.