Monoclonal antibodies against human milk‐fat globule membranes detecting differentiation antigens of the mammary gland and its tumors

TLDR

Developed a panel of 17 monoclonal antibodies against human milk‑fat globule membranes to serve as reagents for diagnosing mammary tumors. The antibodies were characterized by reactivity assays on normal and tumor tissues, in vitro cell lines, and electron‑microscopic localization, revealing nine distinct epitopes on six HMFGM molecules. The panel demonstrated broad binding to resting mammary gland, breast tumors, and various epithelial cells, with one antibody recognizing most carcinomas and metastases but not other tumor types, showing that while individual antibodies lack specificity, the combined panel improves differential diagnosis of mammary tumors.

Abstract

Abstract Mouse monoclonal antibodies have been raised against human milk‐fat globule membranes (HMFGM) to obtain reagents for mammary tumor diagnosis. A panel of 17 anti‐HMFGM antibodies was selected for further investigation. Antibody‐blocking studies indicated that with these antibodies at least nine different non‐overlapping epitopes could be distinguished on six differend molecules, MAM‐1 to MAM‐6. Electron microscopic studies of the cellular localization of the antigens detected by some of these antibodies revealed that they were present on the cell membrane mainly, on the microvilli, lining intercellular and intracytoplasmic lumina. The reactivity of the antibodies was studied on normal and tumor tissues and on in vitro cell lines. All antibodies reacted with the resting mammary gland while eight antibodies also bound to breast tumors. None of the antibodies was specific for the mammary gland or its tumors only, but most antibodies also reacted with other epithelial cells, especially of secretory tissues. When tested on a variety of cell lines a distribution reflecting the tissue distribution could be demonstrated. One of the antibodies reacted with nearly all carcinomas and their metastases and did not react with lymphomas, sarcomas, neuroblastomas, melanomas or nervous system tumors. The specificity of the antibodies, tested individually, was not sufficient for further differential diagnosis of the carcinomas, but when some of these antibodies were used in a panel they contribute to an important improvement of the diagnosis.