Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma.
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.
de Nooij-van Dalen
Arnolda G
AG
Section Tumor Biology, Department of Otolaryngology/Head-and-Neck Surgery, Vrije University Medical Center, Amsterdam, the Netherlands.
van Dongen
Guus A M S
GA
Smeets
Serge J
SJ
Nieuwenhuis
Eline J C
EJ
Stigter-van Walsum
Marijke
M
Snow
Gordon B
GB
Brakenhoff
Ruud H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001853:Bone Marrow / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis; D003937:Diagnosis, Differential; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D017931:DNA Primers; D015342:DNA Probes; D004273:DNA, Neoplasm