Functional heterogeneity correlates with structural heterogeneity of breast carcinoma acid-soluble glycoproteins

Patients with malignant tumors, specifically with metastatic breast carcinoma (BCa), are immunosuppressed and have defective lymphocyte responsiveness to antigenic and mitogenic stimulation. The present study examined the role of perchloric acid (PCA)-soluble glycoproteins and their oligosaccharide moieties from tumor cells and from sera of patients with metastatic BCa. Sera from 15 patients and from age-matched healthy adults were examined for immunoregulatory glycoproteins. BCa tissue was obtained from 9 of the 15 patients. The PCA extracts from tumor tissue were resolved into six (GP-I to GP-VI), and from serum into three (GP-II, GP-IV, and GP-V), BCa-associated glycoproteins. After alkaline borohydride treatment, six groups of BCa-associated oligosaccharides were obtained. Peripheral blood mononuclear (MNC) and natural killer (NK) cells were obtained from patients with metastatic BCa and from age-matched healthy adults. These were used as effector cells in the well-established 4-hr cytotoxicity assay. The results indicated that interleukin 2 (IL-2) significantly (P less than 0.001) enhanced the cytotoxic activities of MNC and NK cells from healthy adults, but it had a nonsignificant effect on MNC and NK cells from patients with metastatic BCa. The BCa-associated glycoproteins and their oligosaccharides varied in their effects on MNC and NK cells from both the healthy adults and the patients with metastatic BCa. IL-2 activated MNC cytotoxic activity against BCa cells. GP-I, GP-II, GP-III, and GP-IV inhibited MNC inherent cytotoxicity and blocked MNC stimulation by IL-2, GP-IV fraction had a statistically nonsignificant effect, whereas GP-V enhanced both MNC inherent and IL-2-activated cytotoxic activities. Oligosaccharides obtained from PCA extracts of BCa tissue and by alkaline borohydride treatment differentially bound and inhibited a series of monoclonal antibodies raised against BCa-associated glycoproteins. These results indicated that the oligosaccharide moieties of the BCa-associated glycoproteins modulate recognition of the BCa cells by the effector cells.