Paret Claudia, Bourouba Mehdi, Beer Alexander, Miyazaki Kaoru, Schnölzer Martina, Fiedler Sabine, Zöller Margot
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.
Int J Cancer. 2005 Jul 10;115(5):724-33. doi: 10.1002/ijc.20977.
C4.4A is a member of the Ly6 family, with low homology to uPAR. It has been detected mainly on metastasizing carcinoma cells and proposed to be involved in wound healing. So far, C4.4A has been observed as an orphan receptor, and its functional activity has not been explored. Using recombinant rat C4.4A (rrC4.4A) made in a eukaryotic expression system, we demonstrate by immunohistology that C4.4A ligands are strongly expressed in tissues adjacent to squamous epithelia of, e.g., tongue and esophagus, the expression pattern partly overlapping with laminin (LN) and complementing the C4.4A expression that is found predominantly on the basal layers of squamous epithelium. ELISA screening of several components of the extracellular matrix revealed selective binding of rrC4.4A to LN1 and LN5 and that transfection of the BSp73AS tumor line with C4.4A cDNA (BSp73AS-1B1) promoted LN1 and LN5 binding. Binding of BSp73AS-1B1 to LN5 and, less markedly, LN1 induced spreading, lamellipodia formation and migration. C4.4A also associates with galectin-3 in nontransformed tissues and tumor lines. There is evidence that the association of C4.4A with galectin-3 influences LN adhesion. C4.4A was described originally as a metastasis-associated molecule. Our findings that LN1 and LN5 are C4.4A ligands, that galectin-3 associates with C4.4A and that C4.4A ligand binding confers a migratory phenotype are well in line with the supposed metastasis association.
C4.4A是Ly6家族的成员，与尿激酶型纤溶酶原激活物受体（uPAR）具有低同源性。它主要在转移癌细胞上被检测到，并被认为参与伤口愈合。到目前为止，C4.4A一直被视为孤儿受体，其功能活性尚未被探索。利用在真核表达系统中制备的重组大鼠C4.4A（rrC4.4A），我们通过免疫组织学证明C4.4A配体在例如舌和食管的鳞状上皮相邻组织中强烈表达，其表达模式部分与层粘连蛋白（LN）重叠，并补充了主要在鳞状上皮基底层发现的C4.4A表达。对细胞外基质的几种成分进行酶联免疫吸附测定（ELISA）筛选发现rrC4.4A与LN1和LN5有选择性结合，并且用C4.4A cDNA转染BSp73AS肿瘤细胞系（BSp73AS - 1B1）促进了LN1和LN5的结合。BSp73AS - 1B1与LN5以及不太明显地与LN1的结合诱导了细胞铺展、片状伪足形成和迁移。在未转化组织和肿瘤细胞系中，C4.4A还与半乳糖凝集素 - 3相关联。有证据表明C4.4A与半乳糖凝集素 - 3的关联影响LN黏附。C4.4A最初被描述为一种转移相关分子。我们发现LN1和LN5是C4.4A配体，半乳糖凝集素 - 3与C4.4A相关联，并且C4.4A配体结合赋予迁移表型，这与推测的转移关联非常一致。
