叶酸受体α与卵巢肿瘤  

The Folate Receptor α and Ovarian Cancer

作　　者：周希彬[1] 邱郑[1] 刘欣欣[1] 张娟[1] 何瑶玉[1] 王筱蒙[1] 王旻[1] 

机构地区：[1]中国药科大学生命科学与技术学院分子生物学教研室,江苏南京210009

出　　处：《药物生物技术》2012年第5期458-461,共4页Pharmaceutical Biotechnology

基　　金：中国药科大学中央高校基本科研专项基金(JKQ2011049)

摘　　要：卵巢肿瘤的死亡率为妇科肿瘤之首,积极探索早期卵巢癌的筛查方法和新型治疗药物,对降低死亡率具有重要意义。叶酸受体α(FRα),对叶酸具有高度亲和性。在生理情况下,叶酸受体α仅低度表达于少数正常组织细胞,而在多种人类上皮源性肿瘤中,尤其是卵巢肿瘤中,都可以检测到高水平表达的叶酸受体α。卵巢上皮癌中有90%以上可见叶酸受体α的高表达,其在卵巢肿瘤中的表达水平可高于正常10～100倍。更为重要的是,叶酸受体α在早期卵巢肿瘤中有很高的阳性率。叶酸受体α为一种极具潜力的卵巢癌相关性的肿瘤抗原,可以作为卵巢肿瘤早期诊断标志物,以及卵巢肿瘤被动免疫治疗的靶点。Ovarian cancer is the fifth leading cause of cancer death and has the highest mortality rate of all gynecologic malignancies. The majority of patients with ovarian cancer present with advanced disease （ stages III-IV） only have a 5-year survival of 5% 20%. The survival of patients with stages I-II disease ranges from 60% - 90%, depending on tumor grade. It suggests the importance of developing new treatment and the early diagnostic method for ovarian cancer. The folate receptor et （ FRα）, a 38 ku molecule, belongs to the folate receptor （FR） family with high affinity for folates. FRet is anchored to cell membranes through a glycosylphos-phatidylinositol moiety and transports folates via an endoeytic process. FRα exhibits the limited normal tissue distribution but is over- expressed in a spectrum of solid tumors, especially in ovarian cancer. It is reported that FRet overexpressed in 〉 90% of ovarian cancers at levels 10- to 100-fold higher than its normal expression, and the expression level of FRα in ovarian cancers correlates with the grade of malignancy. Even in early stage of ovarian cancer, FRet could be detected, The prevalent expression of FRα in ovarian cancer, among all stages, has stimulated interest in applying it as a early diagnostics biomarker. A number of studies have examined the expression of FRa in malignant tissues by immunohistochemistry. Additionally, an immunoblot assay was employed to confirm ovarian cancer patients demonstraing elevated levels of FRa in the circulation system. Furthermore,therapeutic agents based on FRet have been developed. A humanized monoclonal antibody MORAb- 003 against FRet possesses novel, growth-inhibitory functions on cells overexpressing FRet. In addition, MORAb- 003 elicited robust antibody-dependent cellular cytotoxicity （ ADCC ） and complement-dependent cytotoxicity （CDC） in vitro, and inhibited the growth of human ovarian tumor xenografts in nude mice, The novel folate targeted therapies may hold promise for the majority of women wit

关 键 词：卵巢肿瘤 叶酸受体Α 肿瘤抗原 诊疗靶点 

分 类 号：R737.31[医药卫生—肿瘤]