MONOCLONAL-ANTIBODIES DIRECTED AGAINST A WIDESPREAD ONCOFETAL ANTIGEN - THE ALPHA-FETOPROTEIN RECEPTOR

被引:50
作者
MORO, R
TAMAOKI, T
WEGMANN, TG
LONGENECKER, BM
LADEROUTE, MP
机构
[1] CROSS CANC INST,MOLEC ONCOL PROGRAM,EDMONTON T6G 1Z2,ALBERTA,CANADA
[2] UNIV CALGARY,DEPT MED BIOCHEM,CALGARY T2N 1N4,ALBERTA,CANADA
关键词
ALPHA-FETOPROTEIN; ALPHA-FETOPROTEIN BINDING PROTEIN; ALPHA-FETOPROTEIN RECEPTOR; CANCER MARKERS; HYBRIDOMAS; MONOCLONAL ANTIBODIES; ONCOFETAL ANTIGENS; RECEPTORS; TUMOR MARKERS;
D O I
10.1159/000217864
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Accumulating evidence based on alpha-fetoprotein (AFP) cell binding and uptake has shown the presence of a receptor for AFP on the surface of fetal and neoplastic cells. In order to further study this receptor, monoclonal antibodies (MAbs) made against pooled human mammary tumor membrane extracts were screened for their ability to inhibit the binding of radiolabeled AFP to the Ichikawa and TA3/Ha malignant cell lines. IgM-producing clones 167H.1 and 167H.4 were found to inhibit the binding of AFP to its receptor. Conversely, the MAb reaction was inhibited by an excess of AFP but not by serum albumin at an equal molar concentration. The possibility that these MAbs recognize AFP has been ruled out. In addition, we describe a method for the purification of the AFP receptor which yielded fractions reactive to both 167H.4 and AFP. The results obtained strongly suggest that 167H.1 and 167H.4 are directed against th binding site for AFP on the AFP receptor. Using 167H.4 we found positive immunohistochemical staining in 6/6 human mammary tumor specimens whereas 3/3 benign mammary adenomas were negative. Immunostaining of fetal muscle with either 167H.4 or an anti-AFP antiserum yielded a similar staining pattern. The staining of live Ichikawa cells with 167H.4 showed a surface receptor distribution (capping) similar to the one described in previous reports using labeled AFP. The widespread expression of the AFP receptor observed previously is consistent with the results obtained using the MAbs described herein. The potential use of these MAbs for basic and clinical studies is discussed.
引用
收藏
页码:116 / 130
页数:15
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