Heterogeneity in production, secretion and glycosylation of MUC1 epithelial mucin by primary cultures of ovarian carcinoma

Abstract

The MUCI mucin produced by many adenocarcinomas has functions that may be of biological significance and is of importance clinically as a serum tumour marker and as a candidate target for immunotherapy. Previous studies of MUCI production by ovarian cancers have been limited to immunohis‐tochemical studies of tumour specimens and in vitro studies using cell lines. In this study the biosynthesis, secretion and glycosylation of MUCI were studied in primary cultures of tumour cells obtained from 35 patients with stage 3 ovarian cancer. Although 34 of the 35 tumours produced MUCI in vitro, the concentrations of intracellular and secreted MUCI, as measured by an ELISA using core protein‐reactive antibodies, varied over a wide range. In addition, the amount of secreted MUCI as a proportion of the intracellular concentration varied between tumours. Pulse/chase amino acid labelling studies of MUCI biosynthesis also demonstrated variation in secretion rates. Multivariate regression analysis showed that of the variables tumour size, histological type, grade, ploidy status and intracellular and secreted MUCI concentrations in vitro, only mucin secretion rate was significantly associated with serum mucin concentrations (p < 0.001). Culture of tumour cells for 4 days in the presence or absence of a competitive inhibitor of O‐glycosylation, BAG, showed that the degree of glycosylation of MUCI varied between tumours and that under‐glycosylation was not correlated with production or secretion rates. Our study has shown heterogeneity in the production, secretion and glycosylation of MUCI and a strong correlation between the secretion rate in vitro and the concentration in the serum of patients.