Direct and Tumor Microenvironment Mediated Influences of 5 '-Deoxy-5 '-(Methylthio)Adenosine on Tumor Progression of Malignant Melanoma

Stevens, Axel P. and Spangler, Barbara and Wallner, Susanne and Kreutz, Marina and Dettmer, Katja and Oefner, Peter J. and Bosserhoff, Anja-Katrin (2009) Direct and Tumor Microenvironment Mediated Influences of 5 '-Deoxy-5 '-(Methylthio)Adenosine on Tumor Progression of Malignant Melanoma. JOURNAL OF CELLULAR BIOCHEMISTRY, 106 (2). pp. 210-219. ISSN 0730-2312, 1097-4644

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Abstract

Recent studies have shown that a loss of methylthioadenosine phosphorylase (MTAP) gene expression exerts a tumor-promoting effect, including induction of invasiveness, enhanced cell proliferation, and resistance against cytokines. To date, the molecular mechanisms underlying these effects remain unknown. Since the loss of MTAP expression resulted in induced secretion of 5'-deoxy-5'-(methylthio)adenosine (MTA), we hypothesized that NITA might modulate the observed effects. We first determined MTA levels produced by tumor cells in vitro and in situ by means of stable isotope dilution liquid chromatography tandem mass spectrometry. Subsequently, we revealed induction of matrix metalloproteinase (MMP) and growth factor gene expression in melanoma cells accompanied by enhanced invasion and vasculogenic mimicry. In addition, NITA induced the secretion of basis fibroblast growth factor (bFGF) and MMP3 from fibroblasts and the upregulation of activator protein-1 (AP-1) activity in melanoma cells and fibroblasts. In summary, we demonstrated a tumor-supporting role of MTA. J. Cell. Biochem. 106: 210-219, 2009. (C) 2008 Wiley-Liss, Inc.

Item Type: Article
Uncontrolled Keywords: METHYLTHIOADENOSINE PHOSPHORYLASE GENE; GROWTH-FACTOR; MATRIX METALLOPROTEINASES; MTAP EXPRESSION; RAT HEPATOCYTES; IN-VITRO; CELLS; 5'-METHYLTHIOADENOSINE; INHIBITION; 5'-DEOXY-5'-METHYLTHIOADENOSINE; MALIGNANT MELANOMA; TUMOR MICROENVIRONMENT; METHYLTHIOADENOSINE
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Oct 2020 05:56
Last Modified: 07 Oct 2020 05:56
URI: https://pred.uni-regensburg.de/id/eprint/29524

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