DIFFERENTIAL ANTIBODY REACTIVITY AND CD4 BINDING OF THE MAMMARY-TUMORMARKER PROTEIN GCDFP-15 FROM BREAST CYST AND ITS COUNTERPARTS FROM EXOCRINE EPITHELIA

Analysis of biopsies from breast cancer patients demonstrated that GCD FP-15 (gross cystic disease fluid protein-15) is a specific immunocyto chemical marker of primary and secondary apocrine breast tumors. The p rotein has an amino acid sequence identical to SABP (secretory actin-b inding protein), to PIP (prolactin-inducible protein) and to gp17, a p rotein isolated from human seminal plasma. The latter was found to bin d to CD4, a T-cell co-receptor involved in antigen recognition, thereb y inhibiting the ability of the receptor to interact with the HIV-1 en velope protein gp 120. We compare here the ability of independently pu rified GCDFP-15, SABP and gp 17 and of recombinant PIP both to cross-r eact with a panel of monoclonal antibodies (MAbs) raised against GCDFP -15 or gp17, respectively, and to bind to CD4. We show that, although the various factors share the ability to bind to the panel of antibodi es used, differences in the pattern of MAb recognition can be demonstr ated. By comparing the kinetic constants for binding of GCDFP-15 and g p 17 to CD4 by biosensor technology, significant differences in bindin g affinities were observed between the 2 factors, thus reflecting stru ctural differences. Surface plasmon resonance analysis also showed tha t anti-GCDFP-15 and anti-gp17 antibodies inhibit the binding of CD4 to GCDFP-15 and gp17, respectively, to different extents. Our data thus indicate that, while the various forms of the protein are encoded by t he same cDNA, tissue specificities due to post-translational modificat ions exist. This information may be relevant for developing more sensi tive and accurate tests for the use of GCDFP-15 as a diagnostic mammar y tumor marker and, most importantly, raises the possibility that GCDF P-15 may constitute a breast tumor-specific antigen. Int. J. Concer 78 :76-85, 1998. (C) 1998 Wilev-Liss, Inc.