Genomic organization, incidence, and localization of the SPAN-x family of cancer-testis antigens in melanoma tumors and cell lines.

PURPOSE:Members of the (sperm protein associated with the nucleus mapped to the X chromosome) family of cancer-testis antigens are promising targets for tumor immunotherapy because they are normally expressed exclusively during spermiogenesis on the adluminal side of the blood-testis barrier, an immune privileged compartment. EXPERIMENTAL DESIGN AND RESULTS:This study analyzed the human genomic organization, as well as duanyu1842N-X mRNA and protein expression in somatic and cancer cells. The duanyu1842NX family consists of five genes, one of which is duplicated, all located in a gene cluster at Xq27.1. From the centromere, the arrangement of the five duanyu1842NX genes mapped on one contiguous sequence is -C, -A1, -A2, and -D. Reverse transcription-PCR analyses demonstrated expression of duanyu1842N-X mRNA in melanoma and ovarian cell lines, and virtual Northern analysis established duanyu1842NX gene expression in numerous cancer cell lines. Immunoblot analysis using polyclonal antisera raised against recombinant duanyu1842N-X confirmed the translation of duanyu1842N-X proteins in melanoma and ovarian tumor cell lines. The immunoreactive proteins migrated between M(r) 15,000 and M(r) 20,000 similar to those observed in spermatozoa. Immunoperoxidase labeling of melanoma cells and tissue sections demonstrated duanyu1842N-X protein localization in the nucleus, cytoplasm, or both. Ultrastructurally, in melanoma cells with nuclear the protein was associated with the nuclear envelope, a localization similar to that observed in human spermatids and spermatozoa. Significantly, the incidence of immunostaining was greatest in the more aggressive skin tumors, particularly in distant, nonlymphatic metastatic melanomas. CONCLUSIONS:The data herein suggest that the duanyu1842N-X protein may be a useful target in cancer immunotherapy.

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