Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function

Kerstin Fischer; Verena Lutz; Olaf Wilhelm; Manfred Schmitt; Henner Graeff; Peter Heiss; Tomizo Nishiguchi; Nadia Harbeck; Horst Kessler; Thomas Luther; Viktor Magdolen; Ute Reuning

doi:10.1016/S0014-5793(98)01279-4

Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function

Kerstin Fischer, Verena Lutz, Olaf Wilhelm, Manfred Schmitt, Henner Graeff, Peter Heiss, Tomizo Nishiguchi, Nadia Harbeck, Horst Kessler, Thomas Luther, Viktor Magdolen, Ute Reuning

Research output: Contribution to journal › Article › peer-review

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Abstract

Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [³H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo^19,31uPA_19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF. Copyright (C) 1998 Federation of European Biochemical Societies.

Original language	English
Pages (from-to)	101-105
Number of pages	5
Journal	FEBS Letters
Volume	438
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(98)01279-4
State	Published - 30 Oct 1998

Keywords

Antisense transfection
Cell proliferation
Mitogen
Ovarian cancer
Urokinase-type plasminogen activator
Urokinase-type plasminogen activator receptor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0014-5793(98)01279-4

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Fischer, K., Lutz, V., Wilhelm, O., Schmitt, M., Graeff, H., Heiss, P., Nishiguchi, T., Harbeck, N., Kessler, H., Luther, T., Magdolen, V., & Reuning, U. (1998). Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function. FEBS Letters, 438(1-2), 101-105. https://doi.org/10.1016/S0014-5793(98)01279-4

@article{19eb324f17214e20b5bd3879ce4ccf68,

title = "Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function",

abstract = "Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF. Copyright (C) 1998 Federation of European Biochemical Societies.",

keywords = "Antisense transfection, Cell proliferation, Mitogen, Ovarian cancer, Urokinase-type plasminogen activator, Urokinase-type plasminogen activator receptor",

author = "Kerstin Fischer and Verena Lutz and Olaf Wilhelm and Manfred Schmitt and Henner Graeff and Peter Heiss and Tomizo Nishiguchi and Nadia Harbeck and Horst Kessler and Thomas Luther and Viktor Magdolen and Ute Reuning",

note = "Funding Information: The excellent technical assistance of Hildegard Seibold and Dominik Helmecke is gratefully acknowledged. The authors wish to thank Prof. Dr. J{\"o}rg St{\"u}rzebecher, University of Jena, Germany, for providing us with the specific uPA inhibitors. We are also thankful for the generous gift of the fusion protein ATF-UTI by Prof. Dr. Hiroshi Kobayashi, Hamamatsu University, Japan, and the generous support with ATF-HSA by Dr. He Lu, INSERM, Paris, France. This work was supported by a grant of the Deutsche Krebshilfe e.V. (Dr. Mildred Scheel-Stiftung, W119/94/Ma1). The substantial support by Dr. Richard Hart, American Diagnostica, Greenwich, CT, USA, is highly acknowledged.",

year = "1998",

month = oct,

day = "30",

doi = "10.1016/S0014-5793(98)01279-4",

language = "English",

volume = "438",

pages = "101--105",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "1-2",

}

Fischer, K, Lutz, V, Wilhelm, O, Schmitt, M, Graeff, H, Heiss, P, Nishiguchi, T, Harbeck, N, Kessler, H, Luther, T, Magdolen, V & Reuning, U 1998, 'Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function', FEBS Letters, vol. 438, no. 1-2, pp. 101-105. https://doi.org/10.1016/S0014-5793(98)01279-4

TY - JOUR

T1 - Urokinase induces proliferation of human ovarian cancer cells

T2 - Characterization of structural elements required for growth factor function

AU - Fischer, Kerstin

AU - Lutz, Verena

AU - Wilhelm, Olaf

AU - Schmitt, Manfred

AU - Graeff, Henner

AU - Heiss, Peter

AU - Nishiguchi, Tomizo

AU - Harbeck, Nadia

AU - Kessler, Horst

AU - Luther, Thomas

AU - Magdolen, Viktor

AU - Reuning, Ute

N1 - Funding Information: The excellent technical assistance of Hildegard Seibold and Dominik Helmecke is gratefully acknowledged. The authors wish to thank Prof. Dr. Jörg Stürzebecher, University of Jena, Germany, for providing us with the specific uPA inhibitors. We are also thankful for the generous gift of the fusion protein ATF-UTI by Prof. Dr. Hiroshi Kobayashi, Hamamatsu University, Japan, and the generous support with ATF-HSA by Dr. He Lu, INSERM, Paris, France. This work was supported by a grant of the Deutsche Krebshilfe e.V. (Dr. Mildred Scheel-Stiftung, W119/94/Ma1). The substantial support by Dr. Richard Hart, American Diagnostica, Greenwich, CT, USA, is highly acknowledged.

PY - 1998/10/30

Y1 - 1998/10/30

N2 - Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF. Copyright (C) 1998 Federation of European Biochemical Societies.

AB - Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF. Copyright (C) 1998 Federation of European Biochemical Societies.

KW - Antisense transfection

KW - Cell proliferation

KW - Mitogen

KW - Ovarian cancer

KW - Urokinase-type plasminogen activator

KW - Urokinase-type plasminogen activator receptor

UR - http://www.scopus.com/inward/record.url?scp=0032582802&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(98)01279-4

DO - 10.1016/S0014-5793(98)01279-4

M3 - Article

C2 - 9821967

AN - SCOPUS:0032582802

SN - 0014-5793

VL - 438

SP - 101

EP - 105

JO - FEBS Letters

JF - FEBS Letters

IS - 1-2

ER -

Urokinase induces proliferation of human ovarian cancer cells: Characterization of structural elements required for growth factor function

Abstract

Keywords

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