immunocytochemical localization of urokinase-type plasminogen activator in lewis lung carcinoma

The invasively growing and metasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA.

[1]  K. Danø,et al.  Human endothelial cells contain one type of plasminogen activator , 1984, FEBS letters.

[2]  K. Danø,et al.  Distribution of urokinase-type plasminogen activator immunoreactivity in the mouse , 1984, The Journal of cell biology.

[3]  J. Zeuthen,et al.  Inactive proenzyme to tissue‐type plasminogen activator from human melanoma cells, identified after affinity purification with a monoclonal antibody. , 1984, The EMBO journal.

[4]  L. Ossowski,et al.  Antibodies to plasminogen activator inhibit human tumor metastasis , 1983, Cell.

[5]  S. Kohga,et al.  Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors. , 1983, Cancer research.

[6]  P. L. Carl,et al.  Plasminogen activator in normal and tumor‐bearing mice , 1983, International journal of cancer.

[7]  J. Zeuthen,et al.  Monoclonal antibody to human 66,000 molecular weight plasminogen activator from melanoma cells. Specific enzyme inhibition and one‐step affinity purification. , 1983, The EMBO journal.

[8]  J. Zeuthen,et al.  Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. , 1982, Biochemistry.

[9]  J. Zeuthen,et al.  Plasminogen activating enzyme in cultured glioblastoma cells. An immunofluorescence study with monoclonal antibody. , 1982, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[10]  L. Ossowski,et al.  A proenzyme form of human urokinase. , 1982, The Journal of biological chemistry.

[11]  J. Zeuthen,et al.  Monoclonal antibody that specifically inhibits a human Mr 52,000 plasminogen-activating enzyme. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[12]  O. Matsuo,et al.  Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus , 1981, Nature.

[13]  C. Mattsson,et al.  Dissolution Of Thrombi By Tissue Plasminogen Activator, Urokinase And Streptokinase In An Artificial Circulating System , 1981, Thrombosis and Haemostasis.

[14]  L. Larsson.  A novel immunocytochemical model system for specificity and sensitivity screening of antisera against multiple antigens. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[15]  R. Roblin,et al.  Dexamethasone regulation of plasminogen activator in embryonic and tumor-derived human cells. , 1980, Cancer research.

[16]  D. Williams,et al.  Plasminogen activator in cultured Lewis lung carcinoma cells measured by chromogenic substrate assay. , 1980, British Journal of Cancer.

[17]  D. Collen.  On the Regulation and Control of Fibrinolysis , 1980, Thrombosis and Haemostasis.

[18]  D. Rijken,et al.  Relationship between tissue plasminogen activator and the activators in blood and vascular wall. , 1980, Thrombosis research.

[19]  K. Danø,et al.  Purification and characterization of a plasminogen activator from mouse cells transformed by an oncogenic virus. , 1980, Biochimica et biophysica acta.

[20]  K. Danø,et al.  Inhibition of a plasminogen activator from oncogenic virus-transformed mouse cells by rabbit antibodies against the enzyme. , 1980, Biochimica et biophysica acta.

[21]  E. Hoal,et al.  Molecular species of plasminogen activators secreted by normal and neoplastic human cells. , 1980, Cancer research.

[22]  J. Richie,et al.  Correlation of the production of plasminogen activator with tumor metastasis in B16 mouse melanoma cell lines. , 1980, Cancer research.

[23]  L. Ossowski,et al.  Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue , 1979, Cell.

[24]  E. Wilson,et al.  Secretion of plasminogen activator by normal, reactive and neoplastic human tissues cultured in vitro , 1978, International journal of cancer.

[25]  S. Strickland,et al.  The induction of differentiation in teratocarcinoma stem cells by retinoic acid , 1978, Cell.

[26]  I. Fidler,et al.  Tumor heterogeneity and the biology of cancer invasion and metastasis. , 1978, Cancer research.

[27]  A. Granelli‐Piperno,et al.  A study of proteases and protease-inhibitor complexes in biological fluids , 1978, The Journal of experimental medicine.

[28]  K. Danø,et al.  Serine enzymes released by cultured neoplastic cells , 1978, The Journal of experimental medicine.

[29]  S. Strickland,et al.  Plasminogen activator in early embryogenesis: Enzyme production by trophoblast and parietal endoderm , 1976, Cell.

[30]  L. Holmberg,et al.  Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture , 1976, Nature.

[31]  S. Silverstein,et al.  Immunological analysis of plasminogen activators from normal and transformed hamster cells. Evidence that the plasminogen activators produced by SV40 virus-transformed hamster embryo cells and normal hamster lung cells are antigenically identical , 1975, The Journal of experimental medicine.

[32]  K. Danø,et al.  Fibrinolysis associated with oncogenic transformation. Partial purification and characterization of the cell factor, a plasminogen activator. , 1974, The Journal of biological chemistry.

[33]  D. Rifkin,et al.  PROPERTIES OF PLASMINOGEN ACTIVATORS FORMED BY NEOPLASTIC HUMAN CELL CULTURES , 1974, The Journal of experimental medicine.

[34]  J. Unkeless,et al.  SECRETION OF PLASMINOGEN ACTIVATOR BY STIMULATED MACROPHAGES , 1974, The Journal of experimental medicine.

[35]  D. Rifkin,et al.  AN ENZYMATIC FUNCTION ASSOCIATED WITH TRANSFORMATION OF FIBROBLASTS BY ONCOGENIC VIRUSES , 1973, The Journal of experimental medicine.

[36]  K. V. von Kaulla,et al.  Dissimilarity of human vascular plasminogen activator and human urokinase. , 1971, The Journal of laboratory and clinical medicine.

[37]  A. Fletcher,et al.  Effect of urokinase antiserum on plasminogen activators: demonstration of immunologic dissimilarity between plasma plasminogen activator and urokinase. , 1968, The Journal of clinical investigation.

[38]  R. Porter,et al.  Allotype-related sequence variation of the heavy chain of rabbit immunoglobulin G. , 1968, The Biochemical journal.

[39]  A. Fischer.  Mechanism of the Proteolytic Activity of Malignant Tissue Cells , 1946, Nature.

[40]  S. Kohga,et al.  Plasminogen activator content and secretion in explants of neoplastic and benign human prostate tissues. , 1984, Cancer research.

[41]  E. Holmgren,et al.  Isolation of cDNA sequences coding for a part of human tissue plasminogen activator. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[42]  D. Rijken,et al.  Immunological characterization of plasminogen activator activities in human tissues and body fluids. , 1981, The Journal of laboratory and clinical medicine.

[43]  B. Åstedt,et al.  No crossreaction between circulating plasminogen activator and urokinase. , 1979, Thrombosis research.

[44]  E. Reich.  ACTIVATION OF PLASMINOGEN: A GENERAL MECHANISM FOR PRODUCING LOCALIZED EXTRACELLULAR PROTEOLYSIS , 1978 .

[45]  R. Geran,et al.  PROTOCOLS FOR SCREENING CHEMICAL AGENTS AND NATURAL PRODUCTS AGAINST ANIMAL TUMORS AND OTHER BIOLOGICAL SYSTEMS , 1972 .

[46]  T. Ternynck,et al.  The cross-linking of proteins with glutaraldehyde and its use for the preparation of immunoadsorbents. , 1969, Immunochemistry.

[47]  C. Stock,et al.  Studies in a tumor spectrum. III. The effect of phosphoramides on the growth of a variety of mouse and rat tumors. , 1955, Cancer research.