Roles of plasminogen activator inhibitor-1 and -2, and receptor of urokinase-type plasminogen activator (u-PA) in tumor growth and metastasis

Summary

Aim: Roles of urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR), and its inhibitors (PAI-1 and PAI-2) in colon and breast cancer growth and metastasis were investigated. Methods: Antigen levels of u-PA, u-PAR, PAI-1 and PAI-2 were measured in lung tumor sites and its normal neighboring tissues and metastasis sites. mRNA of these factors was measured by Northern blotting and localization of these factors was measured by in situ hybridization. Results: Antigen levels of u-PA, u-PAR, PAI-1 and PAI-2 were higher in both lung and colon cancer tissues than in normal tissues. mRNAs of u-PA, u-PAR, PAI-1 and PAI-2 were all detected in lung cancer tissues. The amounts of u-PA and PAI-2 mRNA were significantly higher in lung cancer tissues than in normal lung tissues. Both u-PAR and PAI-1 levels were significantly higher in large than in small colon tumors. Higher levels of u-PAR were found an independent prognostic value by multivariate analysis. Conclusion: Antigens and mRNAs of u-PA, u-PAR, PAIs were found in tumor tissues.

Zusammenfassung

Studienziel: Untersucht wurde die Bedeutung des Urokinase-Plasminogen-Aktivators (u-PA), seines Rezeptors (u-PAR) und seiner Inhibitoren (PAI-1 und PAI-2) für das Wachstum und die Metastasierung von Kolon- und Mammakarzinomen. Methodik: Die Antigenspiegel von u-PA, u-PAR, PAI-1 und PAI-2 wurden in Lungentumoren und in gesunden angrenzenden Geweben sowie im Bereich von Metastasen gemessen. Die Messung der mRNA dieser Faktoren erfolgte mit Hilfe des Northern-Blotting-Tests, die Lokalisation dieser Faktoren wurde mittels In-situ-Hybridisierung bestimmt. Ergebnisse: Die Antigenspiegel von u-PA, u-PAR, PAI-1 und PAI-2 lagen in Lungen- und Kolonkarzinomgeweben höher als in normalem Gewebe. In Lungenkarzinomgeweben waren jeweils mRNAs von u-PA, u-PAR, PAI-1 und PAI-2 feststellbar. Die Konzentrationen von u-PA- und PAI-2-mRNA lagen in Lungenkarzinomgeweben signifikant höher als in normalem Lungengewebe. In großen Kolontumoren fanden sich signifikant höhere u-PAR- und PAI-1-Konzentrationen. Eine Multivarianzanalyse zeigte, daß höhere u-PAR-Konzentrationen einen unabhängigen prognostischen Aussagewert haben. Schlußfolgerung: In Tumorgeweben waren Antigene und mRNAs von u-PA, u-PAR, PAIs nachweisbar.

Keywords

Cancer - metastasis - u-PA - u-PAR - PAI-1 - PAI-2

Schlüsselwörter

Krebs - Metastase - u-PA - u-PAR - PAI-1 - PAI-2

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