Das humane, endogene, antimikrobielle Peptid LL-37/hCAP-18 ist ein Wachstumsfaktor für Lungenkrebszellen

Tumorentstehung kann als fehl-regulierte Reparatur gesehen werden. Antimikrobielle Peptide (AMPs) sind Effektormoleküle des angeborenen Immunsystems. Neben dieser Abwehrfunktion spielen zahlreiche antimikrobielle Peptide eine Rolle in der Regulation von Entzündung und Gewebereparierung. Das Ziel die...

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Bibliographic Details
Main Author: Von Haussen, Judith
Contributors: Bals, Robert (Dr. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
Online Access:PDF Full Text
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Cancer development can be viewed as dysregulated repair. Antimicrobial peptides (AMPs) are effector molecules of the innate immune system with direct antimicrobial activity. Beside this host defence function several AMPs play a role in the regulation of inflammation and tissue repair. The aim of the present study was to investigate whether the human cathelicidin AMP LL-37/hCAP-18 is involved in the biology of lung cancer. Human cancer cell lines were found to express the human cathelicidin LL-37/hCAP-18 mRNA and peptide at different levels. Application of exogenous LL-37 at low concentrations to cancer cell lines increased proliferation and growth of anchorage-independent colonies. At the molecular level, LL-37 induced phosphorylation of the epidermal growth factor receptor (EGFR) and activation of downstream MAP kinase signalling pathways. Lung cancer cell lines that stably overexpress the peptide by means of a doxycycline-regulated promoter system also showed a faster growth. When these cell lines were injected subcutaneously into nude mice, cathelicidin overexpression resulted in increased tumourigenicity and the formation of significantly larger tumours. High concentrations of LL-37 resulted in induced cell death. Application of LL-37 in combination with cytostatic drugs resulted in increased cell death. In conclusion, the antimicrobial host defense peptide LL-37/hCAP-18 is involved in the biology of lung cancer.