Liu H, Rajasekaran A K, Moy P, Xia Y, Kim S, Navarro V, Rahmati R, Bander N H
Department of Urology, New York Hospital-Cornell Medical Center, New York 10021, USA.
Cancer Res. 1998 Sep 15;58(18):4055-60.
Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein expressed predominantly by prostate cancer cells. We have characterized four monoclonal antibodies that bind to the extracellular domain of PSMA (Liu et al., Cancer Res., 57: 3629-3634, 1997). Here we report that viable LNCaP cells internalize these antibodies. Laser scanning confocal microscopy reveals that the internalized antibodies accumulate in endosomes, and immunoelectron microscopy reveals that endocytosis of the PSMA-antibody complex occurs via clathrin-coated pits. In addition, a quantitative cell surface biotinylation assay demonstrates that PSMA is constitutively endocytosed in LNCaP cells and that anti-PSMA antibodies increase the rate of internalization of PSMA. These studies suggest that PSMA might function as a receptor mediating the internalization of a putative ligand. The availability of prostate-specific internalizing antibodies should aid the development of novel therapeutic methods to target the delivery of toxins, drugs, or short-range isotopes specifically to the interior of prostate cancer cells.
前列腺特异性膜抗原（PSMA）是一种主要由前列腺癌细胞表达的细胞表面糖蛋白。我们已鉴定出四种与PSMA胞外结构域结合的单克隆抗体（Liu等人，《癌症研究》，57: 3629 - 3634，1997）。在此我们报告，活的LNCaP细胞会内化这些抗体。激光扫描共聚焦显微镜显示内化的抗体聚集在内体中，免疫电子显微镜显示PSMA - 抗体复合物的内吞作用通过网格蛋白包被小窝发生。此外，定量细胞表面生物素化分析表明，PSMA在LNCaP细胞中持续进行内吞作用，并且抗PSMA抗体可提高PSMA的内化速率。这些研究表明，PSMA可能作为一种受体介导假定配体的内化。前列腺特异性内化抗体的可得性应有助于开发新的治疗方法，将毒素、药物或短程同位素特异性地递送至前列腺癌细胞内部。
