A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

•LAT1 is highly expressed in tumors but at low levels in normal tissues.•We examine LAT1 expression and function in malignant melanoma (MM).•LAT1 expression in MM tissues and cell lines is higher than those in normal tissues.•LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM...

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Veröffentlicht in:Biochemical and biophysical research communications 2013-09, Vol.439 (1), p.103-108
Hauptverfasser: Fukumoto, Shinya, Hanazono, Kiwamu, Fu, Dah-Renn, Endo, Yoshifumi, Kadosawa, Tsuyoshi, Iwano, Hidetomo, Uchide, Tsuyoshi
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Sprache:eng
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Zusammenfassung:•LAT1 is highly expressed in tumors but at low levels in normal tissues.•We examine LAT1 expression and function in malignant melanoma (MM).•LAT1 expression in MM tissues and cell lines is higher than those in normal tissues.•LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells.•New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.08.020