Martín-Villar Ester, Scholl Francisco G, Gamallo Carlos, Yurrita Maria M, Muñoz-Guerra Mario, Cruces Jesús, Quintanilla Miguel
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Int J Cancer. 2005 Mar 1;113(6):899-910. doi: 10.1002/ijc.20656.
We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1alpha-2, podoplanin), a small mucin-type transmembrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca(2+)-dependent cell-cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion.
我们报道了编码小鼠PA2.26（T1α-2，血小板反应蛋白）人类同源物的完整cDNA序列，PA2.26是一种小的粘蛋白型跨膜糖蛋白，最初被鉴定为小鼠皮肤癌发生过程中角质形成细胞诱导产生的细胞表面抗原。人类PA2.26基因在几种正常组织如胎盘、骨骼肌、心脏和肺中表达为0.9和2.7 kb的两种转录本。使用针对该蛋白胞外域合成肽产生的特异性多克隆抗体，在约25%（15/61）的人类早期口腔鳞状细胞癌中通过免疫组织化学检测到PA2.26。PA2.26在肿瘤中的分布是异质性的，且常常局限于侵袭前沿。双重免疫荧光和共聚焦显微镜分析显示，PA2.26在肿瘤细胞表面与膜细胞骨架连接蛋白埃兹蛋白共定位，并且其在体内的存在与膜E-钙黏蛋白蛋白表达的下调相关。人类PA2.26在HeLa癌细胞和永生化的HaCaT角质形成细胞中的异位表达促进了埃兹蛋白向细胞边缘的重新分布、细胞表面突起的形成以及降低了Ca(2+)依赖的细胞间黏附性。这些结果表明PA2.26是口腔鳞状细胞癌的一种新型生物标志物，可能参与迁移/侵袭过程。
