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DOI: 10.1055/s-2004-826127
Interleukine und Wachstumsregulation von Melanomzellen
Interleukins and Regulation of Growth of Melanoma CellsPublication History
Publication Date:
03 January 2005 (online)

Zusammenfassung
Im Rahmen eigener experimentellen Untersuchungen in vitro gelang es nachzuweisen, dass IL-8 von humanen Melanomzellen sezerniert wird. Die Blockade der IL-8-Freisetzung mittels neutralisierender Antikörper oder alternativ molekularbiologisch durch Zugabe von IL-8-Sequenz-spezifischen Antisense-Oligonukleotiden belegten die Bedeutung von IL-8 als potenter Wachstumsfaktor für Melanomzellen, der sowohl parakrin als auch autokrin wirken kann. In-situ-Hybridiserungen an Primärtumoren und benignen melanozytären Kontrollen wiesen auf eine gewisse prognostische Relevanz des IL-8-Nachweises beim Melanom hin. Im Nacktmausmodell war durch andere Gruppen eine klare Assoziation mit Wachstumsdynamik und Metastasierung nachweisbar, die in neusten Untersuchungen mit einem humanisierten, IL-8-neutralisierenden Antikörper therapeutisch günstigt beeinflusst werden konnte. Es bleibt abzuwarten, ob dieser Erfolg versprechende Antikörper in naher Zukunft erste klinische Studien erreicht.
Abstract
In a series of in-vitro experiments our group demonstrated that human melanoma cells secrete soluble IL-8. Blockade of IL-8 secretion either by neutralizing antibodies or by molecular biological techniques such as antisense oligomers led to a pronounced growth inhibition of melanoma cells and confirm the role of IL-8 as a paracrine and/or autocrine growth factor. Further in-situ hybridisation on primary melanomas as well as benign melanocytic nevi revealed a correlation between IL-8 expression and cinical parameters such as time-to-progression. Additional work by other groups confirmed a strong association between IL-8 and tumor growth and metastasis in a nude mouse model. In the same model a fully humanized IL-8 neutralizing antibody was able to significantly alter the clinical outcome. It remains to be seen whether these promising antibodies will find their way into the clinic in the near future.
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Prof. Dr. Dirk Schadendorf
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ) an der Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Mannheim
Theodor Kutzer Ufer ·
68135 Mannheim
Email: d.schadendorft@dkfz.de