Melanoma cells constitutively release an anchor-positive soluble form of protectin (sCD59) that retains functional activities in homologous complement-mediated cytotoxicity
Melanoma cells constitutively release an anchor-positive soluble form of protectin (sCD59) that retains functional activities in homologous complement-mediated cytotoxicity
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DOI：
10.1172/jci119638
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发表时间：
1997-09-01
影响因子：
15.9
通讯作者：
Maio, M
中科院分区：
文献类型：
--
作者：
Brasoveanu, LI;Fonsatti, E;Maio, M
Protectin（CD 59）是一种糖基磷脂酰肌醇锚定的细胞膜糖蛋白，在黑素细胞上差异表达，是C介导的黑色素瘤细胞溶解的主要限制因子。在这项研究中，我们报告了CD 59阳性黑色素瘤细胞组成性释放可溶性形式的CD 59（sCD 59），其水平与黑色素瘤细胞的生长和分化密切相关。（r = 0.926; SDS-PAGE分析表明，sCD 59的分子组成与黑色素瘤细胞表达的细胞CD 59的分子组成相似，黑色素瘤释放的sCD 59插入同源细胞的细胞膜，使同源细胞的CD 59表达短暂增加，呈锚阳性。sCD 59具有以下功能：它阻断抗CD 59 mAb YTH 53.1与黑素瘤细胞的结合，并逆转其对C介导的裂解的作用。事实上，mAb YTH 53.1与标量剂量的CD 59阳性但非CD 59阴性黑素瘤细胞的条件培养基预孵育显著降低了细胞的增殖。（P < 0.05），并且以剂量依赖性方式，通过mAb YTH53.1掩蔽细胞CD 59诱导的C介导的抗GD 3致敏的黑素瘤细胞的溶解的增强。总之，这些数据表明，CD 59阳性人黑素瘤细胞释放的可溶形式的CD 59在结构上类似于细胞CD 59，保留其锚定能力，是功能性的，并可能损害临床方法的有效性，以体液免疫治疗人黑素瘤。
Protectin (CD59), a glycosylphosphatidylinositol-anchored cell membrane glycoprotein, is differentially expressed on melanocytic cells and represents the main restriction factor of C-mediated lysis of melanoma cells, In this study, we report that CD59-positive melanoma cells constitutively release a soluble form of CD59 (sCD59), and that its levels directly correlate (r = 0.926; P < 0.05) with the amount of membrane-bound CD59, SDS-PAGE analysis showed that the molecular components of sCD59 are similar to those of cellular CD59 expressed by melanoma cells, Melanoma-released sCD59 is anchor positive since it inserts into cell membranes of homologous cells that transiently increase their expression of CD59, Moreover, sCD59 is functional: it blocks the binding of the anti-CD59 mAb YTH53.1 to melanoma cells and reverses its effects on C-mediated lysis, In fact, preincubation of mAb YTH53.1 with scalar doses of conditioned media of CD59-positive but not of CD59-negative melanoma cells reduced significantly (P < 0.05), and in a dose-dependent fashion, the enhancement of C-mediated lysis of anti-GD3-sensitized melanoma cells induced by the masking of cellular CD59 by mAb YTH53.1. Altogether, these data demonstrate that CD59-positive human melanoma cells release a soluble form of CD59 that is structurally similar to cellular CD59, retains its anchoring ability, is functional, and may impair the effectiveness of clinical approaches to humoral immunotherapy for human melanoma.