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Dicarbonyl-mediated protein modifications affect matrix metalloproteinase (MMP) activity

Proteinmodifizierungen durch Dicarbonyle beeinträchtigen die Matrixmetalloproteinase (MMP)-Aktivität

Zeitschrift für Gerontologie und Geriatrie volume 40, pages 357–361 (2007)Cite this article

Abstract

Advanced age is linked with an increased incidence of epithelial tumours (carcinomas) including lung tumours. However, a slowing rate of the increase of age-specific cancer incidence is demonstrated at very advanced ages, and elderly patients also develop less invasive and metastatic tumours than their younger counterparts. Matrix metalloproteinases (MMPs) are commonly upregulated in the stromal compartment of the carcinoma tissue and are believed to promote invasion and metastasis. As the increased serum and tissue level of advanced glycation end products (AGEs) is a characteristic feature of old humans, our study focused on the impact of AGEs on the activity of MMPs released from lung fibroblasts (WI- 38). The collagen gel zymography technique showed the primary presence of MMP-2 in the conditioned medium of the WI-38 fibroblasts, which was even higher in senescent WI-38 fibroblasts. Subsequent treatment of the WI- 38 conditioned medium with the dicarbonyl compound glyoxal, a highly reactive precursor of the AGE formation, resulted in a dose-dependent reduction of the MMP-2 activity. Therefore, our study suggests that the age-associated increase in AGEs might be one potential host factor responsible for the less invasiveness of tumours at very advanced age.

Zusammenfassung

Mit zunehmendem Alter nimmt auch die Häufigkeit von Tumorerkrankungen zu, wobei die epithelialen Tumore (Karzinome) eine besondere Stellung einnehmen. Die Anzahl der Krebserkrankung stagniert jedoch im sehr hohen Lebensalter. Darüber hinaus sind auch die Aggressivität und die Entstehung von Metastasen bei sehr alten Patienten vermindert. Beim invasiven Wachstum und der Metastasierung des Tumors spielen Matrixmetalloproteinasen (MMPs) eine bedeutende Rolle, die im Stromabereich vieler Tumorgewebe erhöht sind. Da es mit dem zunehmenden Lebensalter auch zum Anstieg von Glykierungsendprodukten, den so genannten AGEs, im Serum und in den Organen kommt, haben wir in unserer Studie den Einfluss der AGEBildung auf die Aktivität der MMPs untersucht. Mit Hilfe der Zymographietechnik konnte ein hoher Gehalt an extrazellulärem MMP-2 in den Zellkulturüberständen von Lungenfibroblasten (WI-38) bestimmt werden. Die MMP-2-Sekretion durch seneszente WI-38-Fibroblasten war zudem höher als die durch prä-seneszente WI-38. Die Behandlung der WI-38-Zellkulturüberstände mit der Dicarbonylverbindung Glyoxal, einem reaktiven Vorläufer der AGE-Bildung, führte zu einer dosisabhängigen Reduktion der MMP-2-Aktivität. Aus diesen Daten können wir schlussfolgern, dass die altersassoziierte Erhöhung von AGEs im Körper ein potentieller Faktor ist, der zur verminderten Aggressivität des Tumorwachstums im sehr hohen Lebensalter beiträgt.

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Affiliations

  1. Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle/Saale, Germany

    B. Bartling, M. Desole, R.-E. Silber & A. Simm

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  1. B. Bartling
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  2. M. Desole
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  3. R.-E. Silber
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  4. A. Simm
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Correspondence to B. Bartling.

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Bartling, B., Desole, M., Silber, RE. et al. Dicarbonyl-mediated protein modifications affect matrix metalloproteinase (MMP) activity. Z Gerontol Geriat 40, 357–361 (2007). https://doi.org/10.1007/s00391-007-0485-8

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  • DOI: https://doi.org/10.1007/s00391-007-0485-8

Key words

  • matrix metalloproteinase
  • dicarbonyls
  • lung cancer

Schlüsselwörter

  • Matrixmetalloproteinase
  • Dicarbonyle
  • Lunge
  • Krebs