fibrin and Carcinoma

Peritoneal metastasis (PM) is a very serious complication of gastrointestinal and gynecological malignancies which is poorly documented. Modified mesothelial cell layer and their microenvironments can favor fibrin deposition for cancer cell adhesion. Scanning and transmission electron microscopy of peritoneal surface and cancer cell clusters from cancer patients was done. Ascites and its impact on mesothelial cells were assessed by cytokine array. Neprilysin, matrix metalloprotease, epithelial mesenchymal transition (EMT) related molecules (E-cadherin, Snail, Slug, Twist, Vimentin and Fibronectin), tissues factor (TF), endothelial protein C receptors (EPCR) were quantified by q-PCR. Fibrin in the simples were stained using anti fibrin F1E1 antibody. Migration ability was assessed by scratch assay. Cell viability and neprilysin activity were analyzed by bioluminescence. Cancer cells-fibrin interaction was investigated by scanning electron microscopy (SEM) and microcinematography (MCG). Mesothelial cells change their morphology after incubation with carcinomatosis peritoneal fluids in vitro. EMT associated with upregulation of neprilysin, matrix metalloproteinase-2, tissue factor and cytokines secretions such as interleukin-6, and 8, hepatocyte growth factor and granulocyte chemotactic protein-2 mRNA and protein were observed. EPCR expression as a natural anticoagulant was decreased. In parallel, carcinomatosis cell clusters extracted from peritoneal fluids were found to be associated with fibrin. Kinetic analysis of cancer cell-fibrin interaction in vitro studied by MCG showed that fiber filaments generated from clots inhibited cancer cell adhesion on fibrin clots. These results indicated that fibrin deposit on the peritoneal surface serve as niches for cancer expansion in carcinomatosis patients.

Topics: Biomarkers; Carcinoma; Cell Line, Tumor; Cells, Cultured; Cytokines; Epithelial-Mesenchymal Transition; Female; Fibrin; Gene Expression; Humans; Immunohistochemistry; Peritoneal Neoplasms; Peritoneum; Tumor Microenvironment

Colorectal cancer is the third most often cause of morbidity and mortality due to cancer in Poland. Thromboembolic complications are common events during the course of the disease. It is well known that hemostatic proteins play an important role in cancer progression. The purpose of the study was to evaluate the in loco interactions among colorecatal cancer and coagulation factors. 21 cases of G2 colorectal adenocarcinoma obtained during surgical resection were examined. Immunohistochemical procedures according to ABC method were employed. Tissue factor (TF) and coagulation factors II, VII, X, IX were observed in cancer cells and except factors II and IX--in tumor associated macrophages. TF was also demonstrated in endothelial cells of small blood vessels. Strong expression of fibrinogen was observed among connective tissue at some distance around malignant tumor while weaker expression was found in tumor stroma. Expression of F(1+2), the by-product of thrombin generation, was revealed in cancer cells, macrophages and in the tumor stroma. The results indicate extravascular activation of blood coagulation in loco in colorectal cancer that is TF-dependent.

Topics: Blood Coagulation; Blood Coagulation Factors; Carcinoma; Colorectal Neoplasms; Factor IXa; Factor VII; Factor X; Fibrin; Fibrinogen; Humans; Immunohistochemistry; Neovascularization, Pathologic; Prothrombin; Thromboplastin

A commercially available monoclonal antibody against human fibrin was used to detect fibrin in canine formalin-fixed, paraffin wax-embedded tissue by applying a slightly modified alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Twenty-eight mammary tumours from six bitches were examined for the presence of fibrin. Thrombi and extravascular fibrin deposits were detected in 15 tumours (12 complex adenocarcinomas, one adenocarcinoma, two solid carcinomas), and a single thrombus was detected in one adenoma; 12 tumours (three adenomas, one complex adenoma, four complex adenocarcinomas and four adenocarcinomas) did not show any staining reaction.

Topics: Adenocarcinoma; Adenoma; Animals; Antibodies, Monoclonal; Carcinoma; Dogs; Female; Fibrin; Immunohistochemistry; Mammary Neoplasms, Animal; Necrosis; Thrombosis

The occurrence and distribution of components of coagulation pathways in situ were determined using immunohistochemical techniques applied to 10 cases of primary carcinoma of the breast, normal breast tissue obtained from two patients undergoing reductive mammoplasty, and three patients with benign breast tumors. Tumor cells stained for factor X and thrombomodulin but not for tissue factor, factor V, factor VII, or factor XIII. Rare nonneoplastic duct epithelial cells stained for thrombomodulin, but these tissues did not otherwise stain for any of these antigens. Macrophages within the tumor stroma stained for tissue factor, factor VII, and factor XIII but not for factor V or factor X. These features of macrophages were the same in malignant and nonmalignant breast tissue. Fibrinogen was present in abundance throughout the connective tissue in breast cancer but not in nonmalignant tissues. By contrast, no staining was observed using fibrin-specific antibodies. These results suggest that an intact coagulation pathway does not exist in breast cancer tissue and that thrombin capable of transforming fibrinogen to fibrin is not generated in significant amounts in this tumor type. While fibrin is not a feature of the connective tissue stroma in breast cancer, it is conceivable that the abundant fibrinogen present in the tumor connective tissue (and factor XIII present in connective tissue macrophages) might contribute to the structural integrity of breast tumor tissues.

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Factor VII; Factor X; Fibrin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; In Vitro Techniques; Thrombin; Transglutaminases

Guerin epithelioma, a highly metastatic tumour implanted to Wistar rats contains two inhibitors of fibrinolysis which can be detected with the use of zymographic techniques. The first one--with Mr about 48000 forms SDS-stable complex with urokinase. The second--with Mr about 7000 inhibits fibrinolytic and amidolytic activity of plasmin.

Topics: Aniline Compounds; Animals; Antifibrinolytic Agents; Carcinoma; Chromogenic Compounds; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrinolysin; Molecular Weight; Neoplasm Transplantation; Neoplasms, Experimental; Oligopeptides; Rats; Rats, Inbred Strains; Urokinase-Type Plasminogen Activator

125I-radiolabeled guinea pig fibrinogen was used to measure the influx (20 min) and accumulation (18 h) of fibrinogen/fibrin in three transplantable carcinomas (Lewis lung, TA3/St mammary, and MOT ovarian) growing in the subcutaneous space of syngeneic mice. Fibrinogen influx and, to an even greater extent, fibrin accumulation were substantially increased in all three tumors, as compared with normal control tissues. A significantly larger fraction of tumor-associated than control tissue radioactivity was insoluble in 3 M urea, a property of cross-linked fibrin. Positive identification of cross-linked fibrin was made by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of tumor extracts. Tumor fibrin deposits were localized by immunoperoxidase staining of tissue sections. Fibrin accumulation was also significantly increased in premalignant hyperplastic alveolar nodules that had been transplanted to cleared mammary fat pads, as compared with normal mammary tissue, and was further increased in primary mammary carcinomas that arose from hyperplastic alveolar nodules. These findings generalize to the mouse the principles that tumor vessels are hyperpermeable to plasma proteins and that fibrin accumulates in transplantable and primary tumors. Further, they demonstrate that tumor fibrin is cross-linked and therefore analogous to the fibrin deposited in thrombi, wounds, and cellular immunity.

Topics: Animals; Carcinoma; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Immunoenzyme Techniques; Mammary Neoplasms, Experimental; Mice; Neoplasm Transplantation; Precancerous Conditions

Topics: Adult; Aged; Carcinoma; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Middle Aged; Neoplasm Metastasis; Plasminogen; Prognosis; Protease Inhibitors; Stomach Neoplasms

The antifibrinolytic action of tranexamic acid (AMCHA) on the growth and metastasis of rabbit V2 carcinoma having high fibrinolytic activity was studied. Upon oral administration of AMCHA, the growth of the tumor and metastasis to the lung tended to be inhibited, and the number of metastatic foci in the regional lymph nodes significantly decreased in the early period of tumor growth. Enhancement of fibrin deposition in the tumor and inhibition of fibrinolytic activity of the tumor were recognized in the AMCHA-treated group. The inhibitory effect of tranexamic acid on fibrin dissolution might interfere with local tumor growth and the release of tumor cells into the vessels.

Topics: Animals; Carcinoma; Cyclohexanecarboxylic Acids; Fibrin; Fibrinolysis; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasms, Experimental; Plasminogen Activators; Rabbits; Tranexamic Acid

Topics: Adult; Afibrinogenemia; Aged; Animals; Carcinoma; Factor XIII Deficiency; Fibrin; Humans; Middle Aged; Neoplasms; Neoplasms, Experimental; Rats; Sulfhydryl Compounds

Topics: Blood Coagulation Tests; Carbon Radioisotopes; Carcinoma; Caseins; Disseminated Intravascular Coagulation; Electrophoresis; Esters; Factor XIII; Fibrin; Fibrinogen; Glycine; Hemagglutination Inhibition Tests; Humans; Leukemia; Sepsis; Serum Globulins; Solubility; Thrombocytopenia

Topics: Adenocarcinoma; Adult; Aged; Alpha-Globulins; Blood Coagulation Disorders; Blood Protein Electrophoresis; Bronchial Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Heparin; Humans; Infusions, Parenteral; Lung Neoplasms; Macroglobulins; Male; Middle Aged; Time Factors

Topics: Adenoma; Carcinoma; Culture Media; Culture Techniques; Cyclohexanecarboxylic Acids; Fibrin; Fibrinogen; Fibrinolysis; Fibroma; Granuloma; Granuloma, Giant Cell; Hemangioma; Humans; Methylamines; Mouth Neoplasms; Neoplasms, Muscle Tissue

Fibrin degradation products (F.D.P.) were determined in the serum of 163 women in whom ovarian tumours had been suspected on palpation at gynaecological examination and who were afterwards examined by laparoscopy or subjected to laparotomy. F.D.P. were found in the serum (0.5-30 mg/100 ml) of 23 (72%) out of 32 patients with malignant tumours. Of 131 patients with benign findings F.D.P. (traces to 2 mg/100 ml) were found in six (4.5%), and in most of these the occurrence of F.D.P. could be explained on other clinical grounds. The findings suggest that the examination of F.D.P. in suspected malignant ovarian tumour may be of diagnostic value.Determination of F.D.P. in malignant ascitic fluid showed very high values, ranging between 40 and 350 mg/ 100 ml. This argues for the occurrence of F.D.P. in the blood being due to an extravascular breakdown of fibrin caused by tumour cells, but they may also be due to thromboplastic and fibrinolytic agents from the tumour entering the blood stream.

Topics: Ascitic Fluid; Carcinoma; Cystadenocarcinoma; Cystadenoma; Electrophoresis; Female; Fibrin; Granulosa Cell Tumor; Humans; Laparoscopy; Laparotomy; Liposarcoma; Mesonephroma; Molecular Weight; Ovarian Neoplasms

Topics: Adenocarcinoma; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Protein Disorders; Carcinoma; Colonic Neoplasms; Fibrin; Hemostatics; Humans; Immunoelectrophoresis; Kidney Neoplasms; Male; Middle Aged; Multiple Myeloma; Papain; Plasmapheresis

Topics: Adenofibroma; Basement Membrane; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Connective Tissue; Epithelium; Female; Fibrin; Fibroblasts; Humans; Microscopy, Electron

Topics: Carcinoma; Carcinoma, Bronchogenic; Diagnosis, Differential; Fibrin; Humans; Lung Neoplasms

Topics: Carcinoma; Fibrin; Fibrinolysis; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Fibrin; Fibrinogen; Humans; Pancreas; Pancreatic Neoplasms; Thrombosis