Loss of epithelial cell surface carbohydrates during experimental oral carcinogenesis in the rat

Abstract

Cell surface glycoconjugates were investigated in a rat model of oral chemical carcinogenesis. The lectins Griffonia simplicifolia (GS-I-B4; specific for a-D-galactosyl end groups) and Ulex europeus (UEA-I; specific for a-L-fucosyl groups) were examined microspectrofluorimetrically in the oral epithelium of rats painted with the carcinogen 4-nitroquinoline N-oxide (4NQO) and compared with those treated with solvent alone. After labelling with GS-I-B4, the fluorescent intensity of the basal and parabasal epithelial cells was significantly less after 9 months of 4NQO treatment and in overt squamous cell carcinomas compared to controls. The fluorescent activity of the spinous epithelial cells in the non-invasive tissues treated with 4NQO and in the well differentiated (sites of keratin elaboration) malignant epithelium of squamous cell carcinomas was unchanged after labelling with UEA-I. UEA-I failed to stain undifferentiated (areas lacking keratin) malignant epithelium. The Cell surface carbohydrates change with malignant transformation (Nicolson, 1976;Hakomori, 1985). It has been demonstrated, for example, that the blood group antigens A & B, which are cell surface glycoconjugates (Hakomori, 1981b), are lost in human malignant and premalignant lesions, and that the precursor H antigen accumulates (Dabelsteen & Pindborg, 1973;Dabelsteen et al., 1975;Dabelsteen et al., 1983; Kuhns & Primus, 1985). The biological significance of such changes in cell surface glycoconjugates is incompletely understood but it has been suggested that changes in cell surface glycoconjugates may disrupt normal processes such as proliferation (Hakomori, 1985), adhesion (Hakomori, 1981a;Okada et al., 1984) and contact inhibition of cell movement (Nicolson, 1974), resulting in disrupted growth control and cellular recognition -features characteristic of malignant neoplasia. What is not clear, however, is whether the changes in cell surface carbohydrates that occur in overt malignancies also act as reliable predictors of impending malignancy.It appears that the acquisition of the malignant phenotype in human oral epithelial malignant lesions is associated with a diminished expression of certain lectin-labelled cell surface sugar residues (Dabelsteen & Mackenzie, 1978;Prime et al., 1985a). Recently, we described the topographical binding of the lectins Griffonia simplicifolia (GS-I-B4; specific for a-Dgalactosyl groups) and Ulex europeus (UEA-I; specific for a-L-fucosyl groups) in rat oral mucosa and demonstrated specificity of the labelling to basal/parabasal and spinous epithelial cells, respectively (Prime et al., 1986b). The lectins GS-I-B4 and UEA-I, therefore, can be used as markers of epithelial differentiation (Brabec et al., 1980) and this makes them ideal probes for the study of cell surface carbohydrate changes in carcinogenesis.Rodent tumours, comparable with human oral carcinomas (Prime et al., 1986a) can be induced by 4-nitroquinoline-Noxide (4NQO) (Wallenius & Lekholm, 1973). Since the tumours develop in all animals after a...

Lectin binding patterns in squamous epithelium in experimentally induced hamster buccal pouch carcinoma

“…The pattern of a reduced staining reaction for sugar residues on epithelial cells during neoplastie tranformation agrees with the concepts of modulation Lectin patterns in DMBA induced carcinogenesis 449 of eell surface structures whieh are associated with tumor cell mobility of the membrane component. This pattern is also consistent with many studies of cell surface changes in oral epithelia that have shown a loss of blood group antigen activity in cases of oral carcinoma (11,16). Thus, the tissue which shows a loss of reaction for Con A, RCA-I, and UEA-I receptors on epithelial eells during carcinogenesis may be an indication of an increased potential for cell mobility.…”

“…glycoproteins and intracytoplasmic proteins are believed to be involved in many of these properties (10)(11)(12)(13)(14)(15)(16),…”

“…Changes in the lectin binding pattern have been noted in studies of tissue sections from various neoplastic and nonneoplastic pathologic conditions (10,11). In addition, demonstration of altered lectin binding pattern by tumor cells has been used to predict the likelihood of both recurrence (12) and the invasive potential (13) of a neoplasm and to distinguish between benign and malignant tumors (14)(15)(16).…”