Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells
Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells
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DOI：
10.1023/a:1006790912877
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发表时间：
1999-01-01
影响因子：
4
通讯作者：
Holzmann, B
中科院分区：
文献类型：
--
作者：
Simins, AB;Weighardt, H;Holzmann, B
肿瘤细胞与内皮和组织基质的相互作用被认为是肿瘤转移形成和发展的关键步骤。为了鉴定介导肿瘤细胞与内皮结合的细胞受体，对小鼠T细胞淋巴瘤来源的表达文库进行了粘附诱导cDNA克隆筛选。我们发现了一种新的细胞粘附促进分子，称为ARM-1（粘附调节分子-1），它与人类m - r110,000肿瘤相关抗原同源。ARM-1 cDNA编码的I型跨膜蛋白由407个氨基酸组成，具有潜在的O和n糖基化位点，不属于任何已知的细胞粘附分子家族。293T人胚胎肾细胞过表达ARM-1可显著增加其对不同内皮细胞的粘附。ARM-1在293T细胞中的表达不改变整合素的表达或β -1整合素介导的细胞粘附。人类乳腺癌细胞系的Northern blot分析显示，与非转移细胞相比，转移细胞的ARM-1 mRNA水平升高了3至5倍。总之，我们已经确定ARM-1是一种新的细胞粘附促进受体，在转移性癌细胞中上调。
Interactions of tumor cells with the endothelium and tissue stroma are considered to be critical steps in metastasis formation and progression of cancer. To identify cellular receptors that mediate the binding of tumor cells to endothelium, a murine T cell lymphoma-derived expression library was screened for adhesion-inducing cDNA clones. We identified a novel cell adhesion-promoting molecule, termed ARM-1 (adhesion regulating molecule-1), which is homologous to a human M-r 110.000 tumor-associated antigen. The ARM-1 cDNA codes for a type I transmembrane protein of 407 amino acids with potential O- and N-glycosylation sites that does not belong to any of the known families of cell adhesion molecules. Overexpression of ARM-1 in 293T human embryonic kidney cells significantly increased adhesion to different endothelial cells. ARM-1 expression in 293T cells did not alter integrin expression or beta 1-integrin-mediated cell adhesion. Northern blot analysis of human breast cancer cell lines revealed 3- to 5-fold elevated ARM-1 mRNA levels in metastatic as compared to non-metastatic cells. In conclusion, we have identified ARM-1 as a novel cell adhesion-promoting receptor that is upregulated in metastatic cancer cells.