Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis
Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis
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DOI：
10.1073/pnas.012425299
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发表时间：
2002-01-08
影响因子：
11.1
通讯作者：
Hirohashi, S
中科院分区：
文献类型：
--
作者：
Ino, Y;Gotoh, M;Hirohashi, S
我们报告了 mAb NCC-3G10 识别的癌症相关细胞膜糖蛋白的克隆和表征。该抗体对多种癌细胞表现出强烈的反应性，但仅对有限数量的正常细胞包括淋巴细胞、内皮细胞和复层鳞状上皮的基底细胞。该抗原的 cDNA 编码 178 个氨基酸，其中包括假定的信号序列、潜在的 O-糖基化胞外结构域、单个跨膜结构域和短胞质尾。根据形态学和 Ca2+ 依赖性细胞聚集测定的结果，将 cDNA 转染到 PLC/PRF/5 肝癌细胞中会导致细胞间粘附性降低。在转染的细胞中，E-钙粘蛋白在蛋白质水平上显着降低，与NCC-3G10识别的抗原的表达水平成反比，但在mRNA水平上没有显着降低。 NCC-3G10 包被的珠子引起的抗原聚集引发了肌动蛋白的积累，表明该抗原与 E-钙粘蛋白之间通过肌动蛋白发生了一些相互作用。当通过将 PLC/PRF/5 细胞注射到脾脏中检查严重联合免疫缺陷小鼠的转移能力时，与对照组相比，转染子形成的转移结节数量明显增多。我们将这种下调 E-钙粘蛋白并促进转移的细胞膜糖蛋白命名为 Dysadherin。
We report the cloning and characterization of a cancer-associated cell membrane glycoprotein recognized by mAb NCC-3G10. The antibody showed strong reactivity to a wide variety of cancer cells, but only to a limited number of normal cells including lymphocytes, endothelial cells, and basal cells of stratified squamous epithelium. The cDNA for the antigen encodes 178 aa, which includes a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Transfection of the cDNA into PLC/PRF/5 liver cancer cells resulted in reduced cell-cell adhesiveness, based on both morphology and results of Ca2+-dependent cell aggregation assay. In transfected cells, E-cadherin was markedly decreased at the protein level in inverse proportion to the expression level of the antigen recognized by NCC-3G10, but not at the mRNA level. Aggregation of the antigen by NCC-3G10-coated beads triggered accumulation of actin, suggesting some interplay between this antigen and E-cadherin through actin. When metastatic ability was examined in severe combined immunodeficient mice by injecting PLC/PRF/5 cells into the spleen, the transfectants formed a markedly higher number of metastatic nodules in comparison with controls. We have named this cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis, dysadherin.