We are currently investigating the morphologic aspects of two areas of the basic cell biology of
cancer:
tumor-specific
surface antigens as targets for
immunotoxins, and the phenomenon of multidrug resistance in
chemotherapy of human
tumors.
Colloidal gold cytochemistry has provided a useful method for the electron-microscopic cytochemical detection of materials endocytosed by cells in culture. This technique has been used to study the internalization pathway of
ligands bound to the surface of
cancer cells, particularly
antibodies for use as immunologic targeting
reagents for the construction of
immunotoxins. These
colloidal gold conjugates with
monoclonal antibodies have demonstrated the internalization of these immunologic
reagents through coated pits and receptosomes, which is a necessary step in the delivery of
immunotoxins into the cell where they can mediate their cell-killing functions. Morphologic methods have been employed for the screening and selection of
monoclonal antibodies reactive with the surface of human
ovarian cancer cells for use as
immunotoxins and have demonstrated the in vivo activity of
immunotoxins made with these
antibodies and Pseudomonas
exotoxin in a nude mouse model system. In other studies, we have employed such
reagents for the immunocytochemical detection of the surface expression of P170, the cell-surface efflux pump
protein responsible for the phenotype of multidrug resistance in
tumor cells, and to investigate the distribution of this
protein by using immunocytochemistry in normal human tissues. These results have suggested a role for P170 in normal cell membrane transport of metabolites in various organ systems.