EXPRESSION OF THE VEROTOXIN RECEPTOR GLYCOLIPID, GLOBOTRIAOSYLCERAMIDE, IN OVARIAN HYPERPLASIAS

The presence of cell surface receptor glycolipid, globotriaosylceramid e (Gb(3)), is essential to confer susceptibility to the E. coli-derive d verotoxin (VT). Our earlier studies showed that Gb(3) is expressed i n ovarian carcinoma cell lines. The Gb(3) content of normal ovary, ben ign and malignant primary ovarian tumors, and their metastases have no w been compared by verotoxin thin-layer chromatogram (TLC) overlay of the glycolipid tissue extracts. FITC-labeled VT1 B subunit binding to frozen tumor sections was also monitored histochemically. Low to undet ectable levels of Gb(3) were found in ''normal'' ovarian tissue. Gb(3) was markedly increased in both benign and malignant tumors, suggestin g that increased Gb(3) may be related to proliferation, rather than ma lignancy per se. Mucinous tumors showed the least Gb(3) elevation; ser ous tumors were variable, showing higher levels of Gb(3) in less diffe rentiated malignant tumors. By far the highest Gb(3) content was obser ved for secondary ovarian metastases and tumors refractory to chemothe rapy. Frozen sections of neoplastic ovarian tissue overlaid with fluor escein-conjugated VT1 B subunit show extensive binding to tumor cells, particularly in poorly differentiated samples and blood vessels adjac ent to, and within, the tumor mass. Tumor foci were stained but stroma l tissue was consistently negative both in primary tumors and metastas es. VT staining of well-differentiated primary ovarian tumor sections was weak, corresponding to their low Gb(3) content, but strong stainin g was observed in sections from a highly differentiated primary tumor from a patient who was unexpectedly refractory to clinical chemotherap y. These studies suggest that verotoxin/Gb(3) targeting may provide th e basis for new treatments for ovarian cancer.