Tissue Plasminogen Activator and Urokinase in Normal, Dysplastic and Cancerous Squamous Epithelium of the Uterine Cervix

G Larsson; Å Larsson; B Åstedt

doi:10.1055/s-0038-1645997

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1987; 58(03): 822-826
DOI: 10.1055/s-0038-1645997

Original Article

Schattauer GmbH Stuttgart

Tissue Plasminogen Activator and Urokinase in Normal, Dysplastic and Cancerous Squamous Epithelium of the Uterine Cervix

G Larsson

^*The Department of Obstetrics and Gynaecology, University Lund, Sweden

,

Å Larsson

^**The Department of Oral Pathology, University Lund, Sweden

,

B Åstedt

^*The Department of Obstetrics and Gynaecology, University Lund, Sweden

› Author Affiliations

Abstract

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Summary

The distribution of tissue plasminogen activator (t-PA) and urokinase (u-PA) was investigated immunohistochemically in squamous epithelium of the uterine cervix, in normal and dysplastic conditions as well as in preinvasive and invasive carcinomas. Normal epithelium showed presence of both t PA and u-PA immunoreactivity only in the superficial cellular layer, whereas in preinvasive lesions they were present in all layers. In sections of normal specimens as well as preinvasive lesions the UK immunoreactivity was weaker compared to that of t-PA. Tnvnsivc lesions showed a patchy distribution of t-PA and u-PA immunoreactivity. Furthermore, it could be demonstrated that stromal cells close to the infiltrating malignant squamous epithelium contained t-PA immunoreactivity and also u-PA immunoreactivity. Further immunohistochemical studies disclosed that these cells were macrophages.

Keywords

Plasminogen activator - Urokinase - Dysplasia - Fibrinolysis - Cervical carcinoma

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References

References
1 Danø K, Andreasen PA, Grpndahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 1985; 44: 139-266
2 Holmberg L, Kristoffersson A-C, Lecander I, Wallén P, Åstedt B. Immunoradiometric quantification of tissue plasminogen activator secreted by fetal organs. Comparison with urokinase. Scand J Clin Lab Invest 1982; 42: 347-354
3 Astedt B, Pandolfi M. On release and synthesis of fibrinolytic activators in human organ culture. Eur J Clin Biol Res 1972; 17: 261-267
4 Wun T-C, Ossowski L, Reich E. A proenzyme form of human urokinase. J Biol Chem 1982; 257: 7262-7268
5 Husain SS, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 1983; 220: 31-38
6 Tissot J-D, Schneider Ph, Hauert J, Ruegg M, Kruithof E KO, Bachmann F. Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase. J Clin Invest 1982; 70: 1320-1323
7 Wun T-C, Schleuning W-D, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 257: 3276-3283
8 Astedt B, Glifberg I, Mattsson W, Trope C. Arrest of growth of ovarian tumor by tranexamic acid. JAMA 1977; 238: 154-155
9 Astedt B. Adjuvant treatment of ovarian carcinoma with tranexamic acid. J Clin Pathol 1980; 33: 74-76
10 Astedt B, Henriksson P, Nilsson I-M, Svanberg L. Regression of hemangioma - thrombocytopenia syndrome. Acta Obstet Gynecol Scand 1982; 62: 479-480
11 Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature 1976; 261: 595-597
12 Rifkin D, Loeb J, Moore G, Reich E. Properties of plasminogen activators formed by neoplastic human cell cultures. J Exp Med 1974; 139: 1317-1328
13 Rijken DC, Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 1981; 256: 7035-7041
14 Mesa-Tejada R, Pascal RR, Fenoglio CM. Immunoperoxidase: A sensitive immunohistochemical technique as a “special Stain” in the diagnostic pathology laboratory. Human Pathol 1977; 8: 313-320
15 Wallen P, Ranby M, Bergsdorf N, Kok P. Purification and characterization of tissue plasminogen activator: on the occurrence of two different forms and their enzymatic properties. In: Progress in Fibrinolysis. Davidson JF, Nilsson I-M, Astedt B. (eds.) Churchill Livingstone; Edinburgh: 1981. 05 16-23
16 Astedt B, Fagher U. Immunoradiometrische Bestimmung des Blut/ Gewebe-Plasminogenaktivators bei der Thrombophilie. Folia Haematol 1984; 4: 475-479
17 Holmberg L, Bladh B, Astedt B. Purification of urokinase by affinity chromatography. Biochim Biophys Acta 1976; 445: 215-222
18 Holmberg L, Lecander I, Persson B, Astedt B. An inhibitor from placenta specifically binds urokinase and inhibits plasminogen activator released from ovarian carcinoma in tissue culture. Biochim Biophys Acta 1978; 544: 128-137
19 Astedt B. No crossreaction between circulating plasminogen activator and urokinase. Thromb Res 1979; 14: 535-539
20 Sternberger LA, Hardy Jr PH, Cuculis JJ, Meyer HG. The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 1970; 18: 315-333
21 Larsson A, Astedt B. Immunohistochemical localisation of tissue plasminogen activator and urokinase in the vessel wall. J Clin Pathol 1985; 38: 140-145
22 Isaacson P, Wright DH. Anomalous staining patterns in immunohistologic studies of malignant lymphoma. J Histochem Cvtochem 1979; 27: 1197-1199
23 Burgdorf W HC, Mukai K, Rosai J. Immunohistochemical identification of factor VIII related antigen in endothelial cells of cutaneous lesions of alleged vascular nature. Am J Clin Pathol 1981; 75: 167-171
24 Schested M, Hou-Jensen K. Factor VIII related antigen as an endothelial cell marker in benign and malignant diseases. Virchows Arch (Pathol Anat) 1981; 391: 217-225
25 Electricwala A, Atkinson T. Purification and properties of plasminogen activators from epithelial cells. Eur J Biochem 1985; 147: 511-516
26 Waller EK, Schleuning W-D. Induction of fibrinolytic activity in HeLa cells by phorbol mvristate acetate. J Biol Chem 1985; 260: 6354-6360
27 Isseroff RR, Fusenig NE, Rifkin DB. Plasminogen activator in differentiating mouse keratinocytes. J Invest Dermatol 1983; 80: 217-222
28 Jensen RH, Bigbee WL, Zimmerman AL, King EB. Plasminogen activator as a diagnostic marker for preneoplastic cells in human gynecologic specimens. Acta Cytol 1979; 23: 105-113
29 Birkedal-Hansen H, Taylor RE. Production of three plasminogen activators and an inhibitor in keratinocyte cultures. Biochim Biophys Acta 1983; 756: 308-318
30 Weiss G, Beller FK. Tissue activator of the fibrinolytic enzyme in the female reproductive system. Obstet Gynecol 1969; 34: 809-819
31 Weiss G, Beller FK. Localisation of fibrinolytic activity in uterine cancer. Am J Obstet Gynecol 1969; 103: 1023-1027
32 Ljungn’r H, Holmberg L, Kjeldgaard A, Nilsson I-M, Åstedt B. Immunological characterization of plasminogen activators in a human vessel wall. J Clin Pathol 1983; 36: 1046-1049
33 Isseroff RR, Rifkin DB. Plasminogen is present in the basal layer of the epidermis (abstr). J Invest Dermatol 1982; 78: 359
34 Morioka S, Jensen PJ, Lazarus GS. Human epidermal plasminogen activator. Exp Cell Res 1985; 161: 364
35 Gröndahl-Hansen J, Nielsen LS, Kristensen P, Gröndahl-Hansen V, Andrcascn PA, Danö K. Plasminogen activator in psoriatic scales is of the tissue type PA as identified by monoclonal antibodies. Br J Dermatol 1985; 113: 257
36 Salo T, Liotta LA, Keski-Oja J, Tuipeeniemi-Hujanen T, Tryggvason K. Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells-role in metastasis. Int J Cancer 1982; 30: 669-673
37 Quigley JP, Martin BM, Goldfarb RH, Scheiner CJ, Muller WD. Involvement of serine proteases in growth control and malignant transformation. In: Hormones and Cell Cultures. Cold Spring Harbor Conferences on Cell Proliferation 1979; 6: 219-238
38 Polverini PJ, Leibovich SJ. Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest 1984; 51: 635-642
39 Vassalli J-D, Dayer J-M, Wohlwend A, Belin D. Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J Exp Med 1984; 159: 1653-1668
40 Saksela O, Tapani H, Vaheri A. Urokinase-type plasminogen activator and its inhibitor secreted by cultured human, monocyte-macrophages. J Cell Physiol 1985; 122: 125-132
41 Schreiber AD, Kelley M, Dziarski A, Levinson AI. Human monocyte functional heterogeneity: monocyte fractionation by discontinuous albumin gradient centrifugation. Immunology 1983; 49: 231-238