Modulated expression of glycoprotein oligosaccharides identifies phenotypic differentiation in squamous carcinomas of the human cervix

Abstract

This study has examined changes in expression of complex oligosaccharides during the development of invasive squamous carcinoma of the human cervix to determine whether particular oligosaccharide structures that might influence the phenotypic behavior of individual human cervical cancers were expressed during neoplasia. An extensive panel of lectins capable of identifying all the core and antennary oligosaccharide structures commonly encountered in human epithelia was chosen to probe a range of 11 benign and 26 malignant cervical tissues, all of the latter being clinically stage I. Lectin histochemistry was performed both before and after tissue desialylation using the enzyme neuraminidase to identify masking of oligosaccharide determinants by sialic acid. Nonneoplastic cervical epithelial cells were found to express only type I antennary structures ( Galβl→3GalNAc-) usually modified by sialic acid linked 2 → 6 to terminal Gal- or GaINAc residues. Type II oligosaccharide structures ( Galβ1→4GlcNAo-) were not identified in these normal tissues. No other terminal antennary modifications were detected on nonneoplastic cervical squamous epithelia. Conversely, neosynthesis of type II oligosaccharides was detected by Erythrina cristagalli (ECG) binding in 50% of the squamous carcinomas. Five terminal antennary modifications were commonly identified in the carcinomas that were not identified in normal cervical epithelia and comprised the oligosaccharides bound by lectins RCA, SBA, BS-1, LTA, and UEA-1. Synthesis of these oligosaccharides resulted in expression of structures similar to those recognized as ligands for extracellular matrix-binding proteins. We suggest that expression of such novel oligosaccharide structures may be an important promotor of local invasion and further dissemination of human cervical carcinomas through enhanced binding of malignant cells to stromal matrix proteins. This study has demonstrated that identification of expressed oligosaccharide structures is an objective method of identifying individual tumor cell phenotypes and may form the basis of a useful functional classification of human cervical squamous carcinomas.