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一种新型单克隆抗体 KMP1 通过在体内和体外阻断 CD44 具有潜在的膀胱癌抗肿瘤活性。

A novel monoclonal antibody KMP1 has potential antitumor activity of bladder cancer by blocking CD44 in vivo and in vitro.

机构信息

Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, 650101, China.

Kidney Center, Yunnan Boya Hospital, Kunming, 650228, China.

出版信息

Cancer Med. 2018 May;7(5):2064-2077. doi: 10.1002/cam4.1446. Epub 2018 Mar 25.

Abstract

Bladder cancer becomes a serious medical and social concern due to its high recurrence and mortality rates. Thus, it is urgent to search a novel prognostic biomarker and targeted therapy with high sensitivity and specificity. In this study, we used the human bladder cancer cell line EJ as an immunogen to generate a novel mouse monoclonal antibody KMP1 that specifically bound to bladder cancer, and then, the antitumor effect of KMP1 against bladder cancer was investigated both in vivo and in vitro. The results showed that expression of the KMP1 epitope is consistent with clinical severity and prognosis of bladder cancer. Furthermore, KMP1 not only significantly inhibited the proliferation, migration, and adhesion of EJ cells in vivo, but also suppressed the xenograft tumor growth in nude mice compared with the control group treated with mIgG. Subsequently, the underlying mechanism of KMP1 against bladder cancer was explored via antigen affinity chromatography and mass spectrometry. CD44 located on the cytomembrane was found as the antigen of KMP1. Using RNA interference technology to knock down CD44 expression, we further identified that KMP1 has the antitumor activity by binding to CD44 and blocking its functions. In conclusion, KMP1 might be valuable for development as a promising specific diagnostic biomarker or targeted agent for bladder cancer.

摘要

膀胱癌因其高复发率和死亡率而成为严重的医学和社会问题。因此,迫切需要寻找一种新型的、具有高灵敏度和特异性的预后生物标志物和靶向治疗方法。在本研究中,我们使用人膀胱癌细胞系 EJ 作为免疫原,产生了一种新型的小鼠单克隆抗体 KMP1,该抗体特异性结合膀胱癌,然后研究了 KMP1 对膀胱癌的体内和体外抗肿瘤作用。结果表明,KMP1 表位的表达与膀胱癌的临床严重程度和预后一致。此外,KMP1 不仅显著抑制了 EJ 细胞在体内的增殖、迁移和黏附,而且与对照组相比,用 mIgG 处理后,明显抑制了裸鼠的异种移植肿瘤生长。随后,通过抗原亲和层析和质谱技术探索了 KMP1 对抗膀胱癌的潜在机制。发现位于细胞质膜上的 CD44 是 KMP1 的抗原。利用 RNA 干扰技术敲低 CD44 的表达,我们进一步证实 KMP1 通过与 CD44 结合并阻断其功能发挥抗肿瘤活性。总之,KMP1 可能作为一种有价值的特异性诊断生物标志物或针对膀胱癌的靶向药物进行开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2d2/5943472/064f853c3903/CAM4-7-2064-g001.jpg

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