CELL-SURFACE ANTIGENS OF HUMAN MELANOCYTES AND MELANOMA - EXPRESSION OF ADENOSINE-DEAMINASE BINDING-PROTEIN IS EXTINGUISHED WITH MELANOCYTE TRANSFORMATION
CELL-SURFACE ANTIGENS OF HUMAN MELANOCYTES AND MELANOMA - EXPRESSION OF ADENOSINE-DEAMINASE BINDING-PROTEIN IS EXTINGUISHED WITH MELANOCYTE TRANSFORMATION
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DOI：
10.1084/jem.167.1.197
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发表时间：
1988-01-01
影响因子：
15.3
通讯作者：
EISINGER, M
中科院分区：
文献类型：
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作者：
HOUGHTON, AN;ALBINO, AP;EISINGER, M
黑色素瘤的发病机制经历了多个阶段，从黑素细胞的良性增殖到获得侵袭组织和转移的能力。在对黑素细胞和黑色素瘤细胞表面抗原表达的研究中，我们发现了一个在培养的正常黑素细胞中表达但在黑色素瘤细胞系中不表达的抗原系统。抗该抗原的单抗在黑素细胞上检测到一个120kD的细胞表面糖蛋白。该分子此前已被鉴定为腺苷脱氨酶结合蛋白。来自正常胎儿、新生儿、成人皮肤和成人脉络膜的51个黑素细胞系表达ADAbp，而来自原发和转移性病变的102个黑色素瘤细胞系不表达ADAbp。对放射性标记的牛腺苷脱氨酶的研究证实，黑素细胞表达腺苷脱氨酶的结合部位，但在培养的黑色素瘤细胞上没有检测到结合部位。进一步的研究表明，ADAbp+的黑素细胞在体外恶性转化后成为ADAbp-。对一组冰冻组织的免疫组织化学研究显示，抗ADAbp单抗可与表皮黑素细胞和良性交界性痣反应，但不与潜在的癌前发育不良痣或原发/转移性黑色素瘤病变反应。这些研究表明，ADAbp的表达随着黑素细胞的恶性转化而丢失，推测是在转化过程的早期阶段。
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.