Matrix-Metalloproteinasen und deren Inhibitoren bei Lungenkarzinomen mit malignem Pleuraerguss

Zusammenfassung

Matrix-Metalloproteinasen (MMP) und deren Inhibitoren, tissue inhibitors of metalloproteinases (TIMP), spielen eine wesentliche Rolle beim physiologischen und pathologischen Umbau von Geweben. Ziel dieser Studie war, das Vorkommen von MMP und TIMP bei Patienten mit Lungenkarzinomen und malignem Pleuraerguss (CA) zu bestimmen. Methoden: Die Konzentrationen von MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 und TIMP-2 wurden in Pleuraergussflüssigkeit und Plasma von 31 Patienten mit CA und 14 mit chronischer Herzinsuffizienz (CHF) und in Plasma von 18 Gesunden (CON) mittels ELISA und Zymographie bestimmt. Ergebnisse: ELISA-Konzentrationen von MMP-2, TIMP-1 und TIMP-2 waren in CA Pleuraflüssigkeit vs. CA Plasma erhöht (p < 0,005, p < 0,005, p < 0,05), im Gegensatz zu MMP-9 mit erhöhten Werten im Plasma (p < 0.005). MMP-1 and MMP-8 fand sich in CA vs. CHF Pleuraflüssigkeit erhöht (p < 0,05, p < 0,005). MMP und TIMP zeigten keinen Unterschied der Plasma-Konzentrationen in CA vs. CHF, dagegen waren MMP-9, TIMP-1 und TIMP-2 erhöht vs. CON (jeweils p < 0,005). Die MMP-9/MMP-2-Zymography-Quotienten waren in CA Plasma vs. Ergussflüssigkeit, in CA vs. CHF Plasma und CA vs. CHF Ergussflüssigkeit (jeweils p < 0,005) und in CA vs. CON Plasma erhöht (p < 0,05). Schlussfolgerung: MMP-2-, TIMP-1- und TIMP-2-Konzentrationen finden sich bei CA und CHF im Pleuraraum erhöht, vermutlich als Folge einer unspezifischen pleuralen Reaktion. MMP-1 und MMP-8 finden sich nur in zellreichen CA Pleuraergüssen erhöht. Die Bestimmung der MMP-9/MMP-2 Quotienten in Pleuraergüssen könnte zur Differenzierung von CHF und CA Ergüssen beitragen.

Abstract

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play a crucial role in physiological and pathological matrix turnover. This study aimed to determine the occurrence of MMP and TIMP in lung cancer patients with malignant pleural effusions (CA). Methods: MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF) patients and in plasma of 18 healthy controls (CON). Results: MMP-2, TIMP-1, and TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p < 0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p < 0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p < 0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p < 0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA vs. CON plasma (p < 0.05). Conclusions: MMP-2, TIMP-1, and TIMP-2 accumulate in the pleural compartment in CA and CHF, probably reflecting an unspecific pleural reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to differentiate CHF from CA effusions.

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