Chuong C M, Jiang T X, Yin E, Widelitz R B
Department of Pathology, School of Medicine, University of Southern California, Los Angeles 90033.
Dev Biol. 1994 Aug;164(2):383-97. doi: 10.1006/dbio.1994.1208.
Cloning of human DCC (deleted in colorectal carcinoma, Fearon et al., 1990) showed that it is an immunoglobulin superfamily member homologous to neural cell adhesion molecules (N-CAM). To explore the normal function of this molecule, we have cloned a chicken homologue to DCC (cDCC) and raised an antibody to DCC. cDCC is a protein of 160 kDa with an expression pattern distinct from those of other immunoglobulin family members including N-CAM and Ng-CAM. Transgene expression of cDCC in fibroblasts led to increased cell-cell adhesion. Localization studies in chicken and mouse embryos showed that DCC is expressed in the epithelia of skin, gut, lung, and bladder. In adult, the expression of DCC is limited to the basal layer of stratified epithelium in skin, crypt regions of intestinal villi, and stem cells in mammary duct. Cell aggregation assay using embryonic chicken skin epithelial cells and antibody to DCC showed it is a Ca2+ independent cell adhesion molecule. In epithelial-mesenchymal interactions during feather morphogenesis, antibody to DCC suppressed the formation of dermal condensations and the polarized localization of N-CAM and fibronectin. These results implied that DCC is an epithelial cell adhesion molecule required for mediating critical functions in epithelial-epithelial and epithelial-mesenchymal interactions.
人DCC(结直肠癌缺失基因,费伦等人,1990年)的克隆表明,它是一种与神经细胞黏附分子(N-CAM)同源的免疫球蛋白超家族成员。为了探究该分子的正常功能,我们克隆了鸡的DCC同源物(cDCC)并制备了针对DCC的抗体。cDCC是一种160 kDa的蛋白质,其表达模式与包括N-CAM和Ng-CAM在内的其他免疫球蛋白家族成员不同。cDCC在成纤维细胞中的转基因表达导致细胞间黏附增加。在鸡和小鼠胚胎中的定位研究表明,DCC在皮肤、肠道、肺和膀胱的上皮中表达。在成年个体中,DCC的表达仅限于皮肤复层上皮的基底层、肠绒毛的隐窝区域以及乳腺导管中的干细胞。使用鸡胚胎皮肤上皮细胞和针对DCC的抗体进行的细胞聚集试验表明,它是一种不依赖Ca2+的细胞黏附分子。在羽毛形态发生过程中的上皮-间充质相互作用中,针对DCC的抗体抑制了真皮凝聚的形成以及N-CAM和纤连蛋白的极化定位。这些结果表明,DCC是一种上皮细胞黏附分子,在介导上皮-上皮和上皮-间充质相互作用的关键功能中发挥作用。