fibrin and Cell-Transformation--Neoplastic

Topics: Animals; Arteriosclerosis; Cell Adhesion; Cell Membrane; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Collagen; Endocytosis; Endothelium; Extracellular Matrix; Fibrin; Fibronectins; Growth Substances; Humans; Laminin; Lipid Bilayers; Lipoproteins; Lymphocytes; Membrane Proteins; Neoplasm Metastasis; Neoplasms; Oncogenes; Plasminogen Activators; Proteoglycans; Receptors, Cell Surface; Surface Properties

Topics: Animals; Cell Differentiation; Cell Movement; Cell Transformation, Neoplastic; Chemical Phenomena; Chemistry; Collagen; Factor XIII; Fibrin; Fibronectins; Glycosaminoglycans; Hemostasis; Humans; Models, Chemical; Molecular Weight; Oligosaccharides; Phagocytosis; Structure-Activity Relationship; Thrombosis; Transglutaminases

Topics: Arthritis, Rheumatoid; Binding Sites; Cell Transformation, Neoplastic; Collagen; Disseminated Intravascular Coagulation; Fibrin; Fibronectins; Humans; Molecular Weight; Opsonin Proteins; Sepsis; Surgical Procedures, Operative; Wounds and Injuries

The coagulation cascade can be triggered by an extrinsic or intrinsic signal. The response is a highly complex activation sequence of several serine proteases. This physiological event of hemostasis comprises the activation of the kinin system as well as other plasma constituents. As an expression of the dynamic balance between fibrinogenesis and fibrinolysis plasminogen is activated either by proteases deriving from the blood clotting cascade or by its linkage to the kallikrein kinin system. Inhibitors of the fibrinolytic events have to be directed specifically against serine proteases or they may be used to interact with the substrate fibrin thus its degradation is delayed.

Topics: Aminocaproates; Animals; Avian Sarcoma Viruses; Cell Transformation, Neoplastic; Dexamethasone; Factor XII; Fibrin; Fibrinolysin; Fibrinolysis; Hemostasis; Humans; L Cells; Lysine; Mice; Peptide Hydrolases; Plasminogen; Plasminogen Activators; Receptors, Cell Surface; Simian virus 40; Streptokinase; Tranexamic Acid; Urokinase-Type Plasminogen Activator

Malignant pleural mesothelioma (MPM) is a lethal neoplasm for which current therapy is unsatisfactory. The urokinase plasminogen activator receptor (uPAR) is associated with increased virulence of many solid neoplasms, but its role in the pathogenesis of MPM is currently unclear. We found that REN human pleural MPM cells expressed 4- to 10-fold more uPAR than MS-1 or M9K MPM cells or MeT5A human pleural mesothelial cells. In a new orthotopic murine model of MPM, we found that the kinetics of REN cell tumorigenesis is accelerated versus MS-1 or M9K cells, and that REN instillates generated larger tumors expressing increased uPAR, were more invasive, and caused earlier mortality. While REN, MS-1, and M9K tumors were all associated with prominent extravascular fibrin deposition, excised REN tumor homogenates were characterized by markedly increased uPAR at both the mRNA and protein levels. REN cells exhibited increased thymidine incorporation, which was attenuated in uPAR-silenced cells (P < 0.01). REN cells traversed three-dimensional fibrin gels while MS-1, M9K, and MeT5A cells did not. uPAR siRNA or uPAR blocking antibodies decreased REN cell migration and invasion, while uPA and fetal bovine serum augmented the effects. Transfection of relatively low uPAR expressing MS-1 cells with uPAR cDNA increased proliferation and migration in vitro and tumor formation in vivo. These observations link overexpression of uPAR to the pathogenesis of MPM, demonstrate that this receptor contributes to accelerated tumor growth in part through interactions with uPA, and suggest that uPAR may be a promising target for therapeutic intervention.

Topics: Animals; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Fibrin; Gene Expression Regulation, Neoplastic; Humans; Mesothelioma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Pleural Neoplasms; Receptors, Urokinase Plasminogen Activator; RNA Interference; RNA, Messenger; Time Factors; Transfection; Tumor Burden; Up-Regulation; Urokinase-Type Plasminogen Activator

The development of transformed cell lines evolving from an embryo fibroblastic C3H primary culture was followed before and after the ageing crisis using different techniques. By flow cytometry, alteration of subpopulations having different DNA content and altered metabolic activity was observed after the crisis, with the trend to assume a near tetraploid DNA index at higher passages. The fibrin clot retractile activity was lost in all cases during the ageing crisis, but the outcome did not present uniform values of growth characteristics or chromosome number and tumorigenicity appeared to be a nonstable property of the transformed cell lines.

Topics: Animals; Cell Division; Cell Line, Transformed; Cell Transformation, Neoplastic; DNA; Embryo, Mammalian; Fibrin; Fibroblasts; Flow Cytometry; Karyotyping; Mice; Mice, Inbred C3H; RNA, Double-Stranded

Normal and established human epithelial cell lines obtained from the same organs were compared for their capacity to retract a fibrin clot. Fibrin clot retraction was maximal in normal epithelial cells, reduced in established nontumorigenic lines, and lost in tumorigenic cancer cell lines. Fibrin clot retraction efficiency seemed to be related to the degree of cellular spreading within the clot at the end of the test. Previous works and the present study suggest that fibrin clot retraction is correlated with some steps of cell transformation in vitro.

Topics: Cell Communication; Cell Count; Cell Line; Cell Transformation, Neoplastic; Clot Retraction; Epithelial Cells; Fibrin; Humans; Neoplasms

The expression of transformation parameters (inhibition of cell division during cell crowding, anchorage dependence, loss of fibrin clot retractile activity and secretion of plasminogen activator) was studied in a heterospecific cellular hybrid, made between established L(TK-) cells and the normal human MRC-5 cells. The hybrid nature of the cross was confirmed by the ability to incorporate [3H]-thymidine, by growth in selective HAT medium, by the identification of human chromosomes and by the expression on the surface of 100% of hybrid cells of a human glycoprotein, which is recognized by the 4F2 monoclonal antibody. The hybrid cultures showed cell cycle inhibition which became less stringent with increasing population doublings and the loss of human chromosomes. Fibrin clot retraction and anchorage dependence were absent in spite of the presence of many human chromosomes. The two properties were present or lost simultaneously in the normal parent cells and in the transformed parent or hybrid cells respectively. The human type of plasminogen activator was secreted even with very little human genetic material left, and a complete dissociation between fibrin clot retraction and production of plasminogen activator was observed. The data strengthen the hypothesis that transformation is a multistep process that involves complex genetic control and where cells progressively express different phenotypes and escape growth control.

Topics: Animals; Blood Coagulation; Cell Division; Cell Fusion; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Fibrin; Glycoproteins; Humans; Hybrid Cells; Karyotyping; Kinetics; Mice; Plasminogen Activators

Fibroblast-like cells derived from C3H mice at the first passage in culture, and a line from the same origin, which had undergone spontaneous transformation at the eleventh passage, were seeded on fibrin plates and tested for their attachment and spreading. After 4-24 hours normal cells had a spider-like morphology, while transformed cells remained in round clusters, flattened on the substrate. This data represent the morphological counterpart of the abnormal fibroblast-fibrin interaction shown in a tridimensional model, where transformed cells were found unable to induce the retraction of a fibrin clot (FCR).

Topics: Animals; Cell Adhesion; Cell Movement; Cell Transformation, Neoplastic; Cells, Cultured; Fibrin; Fibroblasts; Mice

Fibrin clot retraction (FCR) was studied in C3H/10T1/2 murine fibroblasts. These cells were able to induce FCR with high efficiency during resting phase as well as during active growth. C3H/10/T1/2 cells which became tumorigenic after X-irradiation lacked FCR activity. Non-tumorigenic revertant clones regained the capacity to induce FCR, while revertants which progressively back-reverted to the neoplastic state showed intermediate FCR activity. These unstable revertants, when again fully tumorigenic, completely lost FCR activity.

Topics: Animals; Cell Line; Cell Transformation, Neoplastic; Clot Retraction; DNA; Fibrin; Fibroblasts; Mice; Mice, Inbred C3H; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental

Topics: Animals; Bile Duct Neoplasms; Buffers; Capillary Permeability; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Cold Temperature; Female; Fibrin; Guinea Pigs; Kinetics; Male; Puromycin; Time Factors

Topics: Animals; Butyrates; Cell Adhesion; Cell Division; Cell Line; Cell Transformation, Neoplastic; Clone Cells; Cricetinae; Enzyme Induction; Fibrin; Mesocricetus

Following treatment of Syrian hamster embryo cells with benzo(a)pyrene, the time required for the expression of enhanced fibrinolytic activity was examined. For this study, the fibrin-agarose overlay method was developed to distinguish the activity of normal and transformed colonies of hamster cells. Colonies possessing enhanced fibrinolytic activity were not observed one passage (2 weeks after treatment). Morphologically transformed colonies, which exhibited no enhanced fibrinolytic activity, were observed 8 days following treatment. In contrast to these two early changes, cells capable of growth in soft agar were observed much later (6 to 8 weeks after treatment). Untreated Syrian hamster embryo cells generally senesced and did not exhibit enhanced fibrinolytic activity. Approximately 1 of 10 untreated cultures escaped senescence and evolved as a continuous cell line; such cultures frequently exhibited enhanced fibrinolytic activity. These results suggest that the acquisition of enhanced fibrinolytic activity, while perhaps not a cause of neoplastic transformation, may reflect a loss of control of the normal function of the cellular genetic apparatus during the process of transformation.

Topics: Benzopyrenes; Cell Transformation, Neoplastic; Cells, Cultured; Clone Cells; Culture Media; Fibrin; Fibrinolysis; Sepharose; Time Factors

Several clones of transformed chick embryo fibroblasts infected with wild-type B77-C or Prague-C strain of Rous sarcoma virus have been isolated from soft agar suspension. These clones were screened for plasminogen activator activity by overlaying monolayer cultures with medium containing agar, casein, and chicken plasminogen. Twenty-three percent of all of the isolated clones showed little caseinolytic activity, 42% had intermediate activity, and 35% had high activity. Although the clones with low plasminogen activator activity had no more than twice the activity shown by uninfected fibroblasts, they did not differ significantly from clones possessing high levels of plasminogen activator in their morphology, 2-deoxyglucose transport, or efficiency of colony formation in soft-agar.

Topics: Avian Sarcoma Viruses; Biological Transport; Cell Division; Cell Transformation, Neoplastic; Clone Cells; Deoxyglucose; Fibrin; Plasminogen Activators

Topics: Cell Transformation, Neoplastic; Cells, Cultured; Clot Retraction; Fibrin; Fibroblasts; Humans; Lung Neoplasms; Skin

Topics: Animals; Blood; Cattle; Cell Transformation, Neoplastic; Cells, Cultured; Cricetinae; Culture Media; Dogs; Fibrin; Fibrinolysin; Fibrinolysis; Fibroblasts; Haplorhini; Humans; Iodine Radioisotopes; Microscopy, Phase-Contrast; Plasminogen; Rabbits; Rats; Simian virus 40; Time Factors

Topics: Animals; Avian Sarcoma Viruses; Cell Fractionation; Cell Transformation, Neoplastic; Chick Embryo; Chromatography, Affinity; Culture Media; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Fibrin; Fibrinolysis; Fibroblasts; Hydrogen-Ion Concentration; Iodine Radioisotopes; Isoflurophate; Kinetics; Molecular Weight; Peptide Hydrolases; Plasminogen; Sodium Dodecyl Sulfate; Surface-Active Agents; Tritium

Topics: Animals; Cell Transformation, Neoplastic; Collagen; Connective Tissue; Cysts; Dose-Response Relationship, Drug; Fibrin; Hepatic Veins; Injections, Subcutaneous; Kupffer Cells; Liver; Liver Diseases; Liver Neoplasms; Lymphatic System; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron; Mitosis; Monocytes; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Trypan Blue

Topics: Adenocarcinoma; Aged; Brain Neoplasms; Cell Transformation, Neoplastic; Diagnosis, Differential; Fibrin; Hemangiopericytoma; Hemangiosarcoma; Hemosiderin; Humans; Male; Meningioma; Neoplasm Metastasis; Neoplasm Regression, Spontaneous