Girling, Anne Carol; (1990) Evaluation of the monoclonal antibody sm3 - spectrum of reactivity in the breast and at other sites, and value as a clinical imaging agent. Doctoral thesis (M.D.), University College Hospital Medical School.

Text Evaluation_of_the_monoclonal_a.pdf Download (14MB)

Abstract

SM3, a monoclonal antibody raised against the deglycosylated mucin from human skimmed milk (SM stands for stripped mucin) has been evaluated. Its reactivity has been compared with that of HMFG2, a monoclonal antibody reactive with the fully glycosylated mucin. Immunohistochemical studies have shown that the SM3 epitope is highly tumour associated, being expressed in more than 90% of mammary carcinomas and in tumours from other sites. It is virtually undetectable, however, in breast tissue showing secretory change, and present at very low levels in normal resting breast tissue, benign breast lesions and normal tissues from elsewhere in the body. Immunoblotting studies have shown that both in breast cancer cell lines and primary mammary carcinomas, SM3 recognises an epitope carried predominantly on low molecular weight components. The potential use of SM3 in immunolocalisation studies has also been investigated. Radiolabelled antibody has been administered pre-operatively to breast cancer patients in an attempt to detect axillary lymph node metastases. Although the results of the imaging studies have so far been disappointing, an ideal model system for future studies of this type has been established. The immunohistochemical and immunoblotting data are compatible with recent work showing that the SM3 epitope consists of a five amino acid sequence on the core protein of the milk mucin. It appears that in fully differentiated mammary epithelial cells highly glycosylated mucins are produced in which the SM3 epitope is masked. In malignancy, however, incompletely glycosylated molecules are produced. These have simpler and shorter carbohydrate side chains and the SM3 epitope on the core protein is exposed. These incompletely processed mucin molecules appear to correspond to the lower molecular weight SM3 reactive bands seen in the immunoblots. Work with SM3 has, therefore, led to further understanding of the processing of mucins in normal and malignant epithelial cells.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item