Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma

Authors

  • Arnolda G. de Nooij-van Dalen,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Guus A.M.S. van Dongen,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Serge J. Smeets,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Eline J.C. Nieuwenhuis,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Marijke Stigter-van Walsum,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Gordon B. Snow,

    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
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  • Ruud H. Brakenhoff

    Corresponding author
    1. Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands
    • Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands
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    • Fax: +31-20-4443688


Abstract

The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPI-anchored surface proteins, of which some show tissue-restricted expression patterns. To identify novel human HNSCC-associated Ly-6 members with squamous cell-associated expression patterns, we performed comprehensive gene-screening consisting of BLAST searches within GenBank databases, followed by expression analysis. Using this approach, the Ly-6K gene could be annotated as a novel member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K, PSCA, GML,RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal and malignant squamous cells and in peripheral blood and bone marrow cells, thus limiting its applicability as an HNSCC-associated marker. In contrast, besides the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected. These data justify further evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of HNSCC. © 2002 Wiley-Liss, Inc.

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