Abstract
It has been proposed that the pathogenesis of melanoma proceeds through multiple stages, ranging from benign proliferation of melanocytic cells to acquisition of the capacity to invade tissues and metastasize. During investigations of cell surface antigens expressed by melanocytes and melanoma, we identified an antigen system that was expressed by cultured normal melanocytes but not by melanoma cell lines. mAbs against this antigen detected a 120-kD cell surface glycoprotein on melanocytes. This molecule had been identified previously as the binding protein for adenosine deaminase (ADAbp). ADAbp was expressed by 51 melanocyte cell lines derived from normal fetal, newborn, and adult skin and adult choroid, but not by 102 melanoma cell lines derived from primary and metastatic lesions. Studies with radiolabeled bovine adenosine deaminase, confirmed that melanocytes expressed binding sites for adenosine deaminase, but no binding sites were detected on cultured melanoma cells. Further studies showed that ADAbp+ melanocytes became ADAbp- upon malignant transformation in vitro. Immunohistochemical studies on a panel of frozen tissues demonstrated reactivity of anti- ADAbp mAbs with epidermal melanocytes and benign junctional nevi, but not with potentially premalignant dysplastic nevi or primary/metastatic melanoma lesions. These studies demonstrate that ADAbp expression is lost with malignant transformation of melanocytes, presumably at an early stage in the transformation process.
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- Albino A. P., Houghton A. N., Eisinger M., Lee J. S., Kantor R. R., Oliff A. I., Old L. J. Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses. J Exp Med. 1986 Nov 1;164(5):1710–1722. doi: 10.1084/jem.164.5.1710. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andy R. J., Finstad C. L., Old L. J., Lloyd K. O., Kornfeld R. The antigen identified by a mouse monoclonal antibody raised against human renal cancer cells is the adenosine deaminase binding protein. J Biol Chem. 1984 Oct 25;259(20):12844–12849. [PubMed] [Google Scholar]
- Andy R. J., Kornfeld R. The adenosine deaminase binding protein of human skin fibroblasts is located on the cell surface. J Biol Chem. 1982 Jul 25;257(14):7922–7925. [PubMed] [Google Scholar]
- Balaban G. B., Herlyn M., Clark W. H., Jr, Nowell P. C. Karyotypic evolution in human malignant melanoma. Cancer Genet Cytogenet. 1986 Jan 1;19(1-2):113–122. doi: 10.1016/0165-4608(86)90378-x. [DOI] [PubMed] [Google Scholar]
- Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
- Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
- Bröcker E. B., Suter L., Brüggen J., Ruiter D. J., Macher E., Sorg C. Phenotypic dynamics of tumor progression in human malignant melanoma. Int J Cancer. 1985 Jul 15;36(1):29–35. doi: 10.1002/ijc.2910360106. [DOI] [PubMed] [Google Scholar]
- Carey T. E., Takahashi T., Resnick L. A., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3278–3282. doi: 10.1073/pnas.73.9.3278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark W. H., Jr, Elder D. E., Guerry D., 4th, Epstein M. N., Greene M. H., Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984 Dec;15(12):1147–1165. doi: 10.1016/s0046-8177(84)80310-x. [DOI] [PubMed] [Google Scholar]
- Cordon-Cardo C., Finstad C. L., Bander N. H., Melamed M. R. Immunoanatomic distribution of cytostructural and tissue-associated antigens in the human urinary tract. Am J Pathol. 1987 Feb;126(2):269–284. [PMC free article] [PubMed] [Google Scholar]
- Daddona P. E., Kelley W. N. Human adenosine deaminase. Stoichiometry of the adenosine deaminase-binding protein complex. Biochim Biophys Acta. 1979 Oct 24;580(2):302–311. doi: 10.1016/0005-2795(79)90143-0. [DOI] [PubMed] [Google Scholar]
- Dippold W. G., Lloyd K. O., Li L. T., Ikeda H., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: definition of six antigenic systems with mouse monoclonal antibodies. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6114–6118. doi: 10.1073/pnas.77.10.6114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisinger M., Marko O., Ogata S., Old L. J. Growth regulation of human melanocytes: mitogenic factors in extracts of melanoma, astrocytoma, and fibroblast cell lines. Science. 1985 Sep 6;229(4717):984–986. doi: 10.1126/science.4023718. [DOI] [PubMed] [Google Scholar]
- Eisinger M., Marko O. Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2018–2022. doi: 10.1073/pnas.79.6.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finstad C. L., Cordon-Cardo C., Bander N. H., Whitmore W. F., Melamed M. R., Old L. J. Specificity analysis of mouse monoclonal antibodies defining cell surface antigens of human renal cancer. Proc Natl Acad Sci U S A. 1985 May;82(9):2955–2959. doi: 10.1073/pnas.82.9.2955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halaban R., Alfano F. D. Selective elimination of fibroblasts from cultures of normal human melanocytes. In Vitro. 1984 May;20(5):447–450. doi: 10.1007/BF02619590. [DOI] [PubMed] [Google Scholar]
- Herlyn M., Balaban G., Bennicelli J., Guerry D., 4th, Halaban R., Herlyn D., Elder D. E., Maul G. G., Steplewski Z., Nowell P. C. Primary melanoma cells of the vertical growth phase: similarities to metastatic cells. J Natl Cancer Inst. 1985 Feb;74(2):283–289. [PubMed] [Google Scholar]
- Herlyn M., Thurin J., Balaban G., Bennicelli J. L., Herlyn D., Elder D. E., Bondi E., Guerry D., Nowell P., Clark W. H. Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Res. 1985 Nov;45(11 Pt 2):5670–5676. [PubMed] [Google Scholar]
- Holzmann B., Bröcker E. B., Lehmann J. M., Ruiter D. J., Sorg C., Riethmüller G., Johnson J. P. Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes. Int J Cancer. 1987 Apr 15;39(4):466–471. doi: 10.1002/ijc.2910390410. [DOI] [PubMed] [Google Scholar]
- Holzmann B., Johnson J. P., Kaudewitz P., Riethmüller G. In situ analysis of antigens on malignant and benign cells of the melanocyte lineage. Differential expression of two surface molecules, gp75 and p89. J Exp Med. 1985 Feb 1;161(2):366–377. doi: 10.1084/jem.161.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghton A. N., Brooks H., Cote R. J., Taormina M. C., Oettgen H. F., Old L. J. Detection of cell surface and intracellular antigens by human monoclonal antibodies. Hybrid cell lines derived from lymphocytes of patients with malignant melanoma. J Exp Med. 1983 Jul 1;158(1):53–65. doi: 10.1084/jem.158.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghton A. N., Eisinger M., Albino A. P., Cairncross J. G., Old L. J. Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med. 1982 Dec 1;156(6):1755–1766. doi: 10.1084/jem.156.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghton A. N., Real F. X., Davis L. J., Cordon-Cardo C., Old L. J. Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells. J Exp Med. 1987 Mar 1;165(3):812–829. doi: 10.1084/jem.165.3.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghton A. N., Taormina M. C., Ikeda H., Watanabe T., Oettgen H. F., Old L. J. Serological survey of normal humans for natural antibody to cell surface antigens of melanoma. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4260–4264. doi: 10.1073/pnas.77.7.4260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghton A. N., Thomson T. M., Gross D., Oettgen H. F., Old L. J. Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. J Exp Med. 1984 Jul 1;160(1):255–269. doi: 10.1084/jem.160.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inwood M., Povey S., Delhanty J. D. Comparison of isozymes in fetal, adult and transformed fibroblasts. Cell Biol Int Rep. 1980 Apr;4(4):327–335. doi: 10.1016/0309-1651(80)90214-3. [DOI] [PubMed] [Google Scholar]
- Johnson J. P., Demmer-Dieckmann M., Meo T., Hadam M. R., Riethmüller G. Surface antigens of human melanoma cells defined by monoclonal antibodies. I. Biochemical characterization of two antigens found on cell lines and fresh tumors of diverse tissue origin. Eur J Immunol. 1981 Oct;11(10):825–831. doi: 10.1002/eji.1830111015. [DOI] [PubMed] [Google Scholar]
- Lehmann J. M., Holzmann B., Breitbart E. W., Schmiegelow P., Riethmüller G., Johnson J. P. Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. Cancer Res. 1987 Feb 1;47(3):841–845. [PubMed] [Google Scholar]
- Pedersen M. I., Bennett J. W., Wang N. Nonrandom chromosome structural aberrations and oncogene loci in human malignant melanoma. Cancer Genet Cytogenet. 1986 Feb 1;20(1-2):11–27. doi: 10.1016/0165-4608(86)90103-2. [DOI] [PubMed] [Google Scholar]
- Pincus T., Hartley J. W., Rowe W. P. A major genetic locus affecting resistance to infection with murine leukemia viruses. IV. Dose-response relationships in Fv-1-sensitive and resistant cell cultures. Virology. 1975 Jun;65(2):333–342. doi: 10.1016/0042-6822(75)90039-2. [DOI] [PubMed] [Google Scholar]
- Schrader W. P., Stacy A. R. Immunoassay of the adenosine deaminase complexing proteins of human tissues and body fluids. J Biol Chem. 1979 Dec 10;254(23):11958–11963. [PubMed] [Google Scholar]
- Trotta P. P., Balis M. E. Characterization of adenosine deaminase from normal colon and colon tumors. Evidence for tumor-specific variants. Biochemistry. 1978 Jan 24;17(2):270–278. doi: 10.1021/bi00595a013. [DOI] [PubMed] [Google Scholar]
- Ueda R., Ogata S., Morrissey D. M., Finstad C. L., Szkudlarek J., Whitmore W. F., Oettgen H. F., Lloyd K. O., Old L. J. Cell surface antigens of human renal cancer defined by mouse monoclonal antibodies: identification of tissue-specific kidney glycoproteins. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5122–5126. doi: 10.1073/pnas.78.8.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van der Weyden M. B., Kelley W. N. Human adenosine deaminase. Distribution and properties. J Biol Chem. 1976 Sep 25;251(18):5448–5456. [PubMed] [Google Scholar]
- ten Kate J., Wijnen J. T., van der Goes R. G., Quadt R., Griffioen G., Bosman F. T., Khan P. M. Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas. Cancer Res. 1984 Oct;44(10):4688–4692. [PubMed] [Google Scholar]
- ten Kate J., van den Ingh H. F., Khan P. M., Bosman F. T. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma. Int J Cancer. 1986 Apr 15;37(4):479–485. doi: 10.1002/ijc.2910370402. [DOI] [PubMed] [Google Scholar]