A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase.
Adenosine deaminase binding protein (ADAbp) is a cell surface glycoprotein that is expressed by normal melanocytes but not by melanoma, the malignant counterpart. ADAbp is specifically downregulated during malignant transformation of melanocytes. Recently, we have developed a system that progressively transforms melanocytes in vitro in defined steps. Transduction with v-Ha-ras oncogene followed by long-term culture leads to a cell phenotype and genotype that specifically mimics human melanoma. Loss of ADAbp expression occurred concomitantly with the emergence of growth factor independence and appearance of specific chromosomal abnormalities. The cellular function of ADAbp has not been defined. To characterize ADAbp, the mature 110-kD form was purified from human kidney. Five tryptic peptides from purified human ADAbp revealed 100% homology to a serine protease, human dipeptidyl peptidase IV (DPP IV), also known as CD26. DPP IV activity was detected in lysates from human melanocytes and renal carcinoma cells but not melanoma cells, and DPP IV activity could be specifically isolated from melanocytes by binding to ADA or to S27 monoclonal antibody against ADAbp. These findings show that ADAbp is a cell surface ectopeptidase that is tightly regulated during neoplastic transformation of melanocytes.
Morrison
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Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Vijayasaradhi
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Engelstein
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Albino
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Houghton
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D000243:Adenosine Deaminase / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D008544:Melanocytes / Q000201:enzymology* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D015531:Radioimmunoprecipitation Assay; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase