Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma of the lung

Abstract

Components of coagulation and fibrinolysis reactions were identified in situ by immunohistochemical staining in fresh frozen sections of small cell carcinoma of the lung tissue. Tumor cells stained positively for tissue factor, a protein that is capable of activating the extrinsic pathway of coagulation (the components of which have been seen within small cell carcinoma of the lung [SCCL] tissue), and for proteins C and S antigens. Fibrin was seen in a focal distribution at the host-tumor interface, indicating that thrombin had acted upon the fibrinogen found throughout the tumor stroma. Staining with a neoepitope-specific antibody, which does not discriminate between fibrinogen fragment D and fibrin fragment D-dimer, was similar to that of the fibrin antibody. High molecular weight urokinase-type and tissue-type plasminogen activators were seen in vascular endothelium, but neither existed within the tumor. Low molecular weight urokinase was found in rare isolated foci of tumor cells primarily adjacent to areas of necrosis. Plasminogen activator inhibitor-3 occurred in tumor cell cytoplasmic blebs and in necrotic tumor cells, but plasminogen activator inhibitors 1 and 2 were not seen. Our data suggest a mechanism for thrombin generation and fibrin formation within SCCL tissues that could support cell proliferation, stroma formation, and preservation. These features could be conductive to perpetuation of this tumor and conceivably could form the basis of the beneficial effects of antithrombotic therapy seen in SCCL.

Inducible expression of tissue factor in small-cell lung cancer: impact on morphology and matrix metalloproteinase secretion

“…We have shown absent or negligible procoagulant activity in a panel of SCLC cell lines (Keller et al 2001). Reports on TF expression in SCLC tumour specimens are rare (Wojtukiewicz et al 1990) and not conclusive probably since SCLC is rarely resected and only limited numbers of specimens are available.…”

Analysis of the saliva proteome from patients with head and neck squamous cell carcinoma reveals differences in abundance levels of proteins associated with tumour progression and metastasis

“…Fibrin may also promote angiogenesis. The fibrin clot and the associated coagulation factors provide a highly pro-angiogenic environment [24] Previous studies documented the presence of fibrin and fibrinogen in situ in small cell carcinoma of the lung, renal cell carcinoma, malignant melanoma, and ovarian carcinoma [25][26][27][28][29][30][31]. In this study it was found that beta fibrin was 2.77 fold increased in abundance levels in the saliva from the patients with HNSCC compared to the control group.…”

Haemostasis Activation Markers in Plasma of Patients with Benign and Malignant Gynaecological Tumours: A Pilot Study

“…The elevated thrombinantithrombin HI levels are consistent with an earlier study on this topic, in which thrombin-antithrombin III was considered a marker of malignant gynaecological disease (17). In general, an explanation for the activation of blood coagulation in tumours is thought to be a direct interaction of the coagulation factors with tumour cells (18,19) or an indirect production of cytokines (20). The evidence for both of these etiologies are however based on immunohistological investigations.…”