Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA.
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):732-7. doi: 10.1073/pnas.0911397107. Epub 2009 Dec 18.
In our effort to find diagnostic markers and to develop therapeutic approaches for prostate cancer, we have identified an mAb that is capable of binding to a cell surface antigen specifically expressed on both androgen-dependent and androgen-independent prostate cancer cells. Immunohistological studies revealed that this mAb, called F77, stained 112 of 116 primary and 29 of 34 metastatic human prostate cancer specimens. Although the mAb F77 alone directly promotes prostate cancer cell death, it also mediates complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. In addition, mAb F77 can significantly inhibit androgen-independent PC3 and Du145 tumor growth in nude mice. Antigen characterization revealed that mAb F77 recognizes a very small molecular species with glycolipid properties. F77 antigen is concentrated in the lipid-raft microdomains, which serve as platforms for the assembly of associating protein complexes. Thus, the present study indicates that mAb F77 defines a unique prostate cancer marker and shows promising potential for diagnosis and treatment of prostate cancer, especially for androgen-independent metastatic prostate cancer.
在寻找前列腺癌的诊断标志物和开发治疗方法的过程中,我们鉴定了一种能够与雄激素依赖性和雄激素非依赖性前列腺癌细胞表面抗原特异性结合的 mAb。免疫组织化学研究表明,这种名为 F77 的 mAb 可以染色 116 例原发和 34 例转移性前列腺癌标本中的 112 例。尽管 mAb F77 本身可以直接促进前列腺癌细胞死亡,但它也介导补体依赖性细胞毒性和抗体依赖性细胞毒性。此外,mAb F77 可以显著抑制裸鼠中的雄激素非依赖性 PC3 和 Du145 肿瘤生长。抗原鉴定表明,mAb F77 识别一种具有糖脂性质的非常小的分子种类。F77 抗原集中在脂筏微区,这些微区是相关蛋白复合物组装的平台。因此,本研究表明 mAb F77 定义了一个独特的前列腺癌标志物,并显示出在诊断和治疗前列腺癌,特别是雄激素非依赖性转移性前列腺癌方面的有希望的潜力。