Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane.
Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane.
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转移相关的 5T4 癌胚抗原集中在质膜的微绒毛投射处。
DOI：
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发表时间：
1995
影响因子：
4
通讯作者：
Peter L. Stern
中科院分区：
文献类型：
--
作者：
C. Carsberg;K. A. Myers;Gareth S. Evans;Terence D Allen;Peter L. Stern
5T4 癌胎儿抗原是一种 72 kDa 糖蛋白，由针对人胎盘滋养层产生的单克隆抗体定义，在许多不同的癌症中表达，但仅在一些正常上皮细胞中检测到低水平。对结直肠癌中表达模式的免疫组织化学分析表明肿瘤细胞中抗原的存在与转移性扩散之间存在显着关联。编码 5T4 分子的 cDNA 已被分离出来，细胞外部分含有几个富含亮氨酸的重复序列，这些重复序列与细胞相互作用有关。为了研究 5T4 分子的细胞生物学作用，在 CMV 立即早期启动子的控制下，用 5T4 cDNA 稳定转染鼠 L 细胞（A9 衍生物）。与单独载体转染的细胞相比，表达5T4的细胞表现出更纺锤形的形态。共聚焦免疫荧光显微镜显示 5T4 抗原表达呈“圆点”模式，细胞之间的强度不均匀，但分布在整个细胞表面。透射和扫描电子显微镜显示，在转染的A9细胞和各种癌细胞系中，5T4抗原集中在质膜的微绒毛突起处。这种突起表达了一系列在细胞粘附和运动中发挥作用的表面分子。在多种癌细胞系中也观察到了 5T4 抗原与微绒毛投射的这种关联。 A9 细胞中的 5T4 表达还与细胞分裂模式的改变、细胞-基质粘附力的降低和细胞运动性的增加有关。这些结果支持了这样的假设：5T4分子可能在滋养层和肿瘤细胞侵袭过程中具有直接功能。
The 5T4 oncofoetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. A cDNA encoding the 5T4 molecules has been isolated and the extracellular portion contains several leucine-rich repeats which have been implicated in cellular interactions. To study the cell biological role of 5T4 molecules, murine L cells (A9 derivative) were stably transfected with 5T4 cDNA under the control of the CMV immediate-early promoter. The 5T4-expressing cells exhibited a more spindle-shaped morphology compared to the vector alone transfected cells. Confocal immunofluorescence microscopy revealed a 'polkadot' pattern of 5T4 antigen expression, heterogeneous in intensity between cells, but distributed over the entire cell surface. Transmission and scanning electron microscopy showed that the 5T4 antigen is concentrated at microvillus projections of the plasma membrane both in the transfected A9 cells and in various carcinoma cell lines. Such projections express an array of surface molecules which function in cell adhesion and motility. This association of 5T4 antigen with microvillus projections was also observed in various carcinoma cell lines. 5T4 expression in A9 cells was also associated with an altered pattern of cell division, decreased cell-substratum adhesion and increased cellular motility. These results support the hypothesis that 5T4 molecules may have a direct function in trophoblast and tumour cell invasion processes.
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DOI：
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