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Titolo:
Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma - A potential mechanism for high tumor aggressiveness
Autore:
Kunz, M; Hartmann, A; Flory, E; Toksoy, A; Koczan, D; Thiesen, HJ; Mukaida, N; Neumann, M; Rapp, UR; Brocker, EB; Gillitzer, R;
Indirizzi:
Univ Wurzburg, Dept Dermatol, D-8700 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-8700 Dermatol, D-8700 Wurzburg, Germany Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, D-8700 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-8700 llforsch, D-8700 Wurzburg, Germany Univ Wurzburg, Inst Pathol, Dept Mol Pathol, D-8700 Wurzburg, Germany UnivWurzburg Wurzburg Germany D-8700 l Pathol, D-8700 Wurzburg, Germany Univ Wurzburg, Inst Immunol, D-8700 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-8700 Immunol, D-8700 Wurzburg, Germany Kanazawa Univ, Dept Mol Pharmacol, Kanazawa, Ishikawa 920, Japan Kanazawa Univ Kanazawa Ishikawa Japan 920 , Kanazawa, Ishikawa 920, Japan Univ Rostock, Dept Immunol, Rostock, Germany Univ Rostock Rostock Germany iv Rostock, Dept Immunol, Rostock, Germany
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 3, volume: 155, anno: 1999,
pagine: 753 - 763
SICI:
0002-9440(199909)155:3<753:AUOIIH>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; INDUCED TRANSCRIPTIONAL ACTIVATION; NECROSIS-FACTOR-ALPHA; FACTOR MESSENGER-RNA; C6 GLIOMA-CELLS; FACTOR-KAPPA-B; BINDING-SITES; NUDE-MICE; IN-VITRO; HYPOXIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Kunz, M Univ Rostock, Dept Dermatol, Augusten Str 80, D-18055 Rostock, Germany Univ Rostock Augusten Str 80 Rostock Germany D-18055 ock, Germany
Citazione:
M. Kunz et al., "Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma - A potential mechanism for high tumor aggressiveness", AM J PATH, 155(3), 1999, pp. 753-763

Abstract

Besides its proinflammatory properties, interleukin-8 (IL-8) has been suggested as an important promoter for melanoma growth. To study the role of IL-8 in melanoma biology, we determined the in vivo expression of IL-8 mRNA by in situ hybridization in primary melanoma lesions and metastases. High levels of melanoma cell-associated IL-8-specific transcripts were exclusivelydetected in close vicinity of necrotic/hypoxic areas of melanoma metastases, whereas both in primary melanomas and in non-necrotic metastases IL-8 expression was low or absent. To analyze further the up-regulation of IL-8 mRNA expression in necrotic/hypoxic tumor areas, human melanoma cell lines ofdifferent aggressiveness exposed to severe hypoxic stress (anoxia) were used as an in vitro model. Anoxia induced IL-8 mRNA and protein expression inthe highly aggressive/metastatic cell lines MV3 and BLM but not in the lowaggressive cell Lines IF6 and 530. As shown by IL-8 promoter-dependent reporter gene analysis and mRNA stability assays, elevated mRNA levels in melanoma cells were due to both enhanced transcriptional activation and enhanced IL-8 mRNA stability. interestingly, transcriptional activation was abolished by mutations in the AP-1 and the NF-kappa B-like binding moths, indicating that both sites are critical for IL-8 induction. Concomitantly, anoxia induced an enhanced binding activity of AP-1 and NF-kappa B transcription factors only in the highly aggressive cells. From our in vitro and in vile data we suggest that anoxia-induced regulation of IL-8 might be a characteristic feature of aggressive tumor cells, thus indicating that IL-8 might play a critical role for tumor progression in human malignant melanoma.

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Documento generato il 20/09/20 alle ore 10:06:49