Cellular sialic acid level and phenotypic expression in B16 melanoma cells: Comparison of spontaneous variations and bromodeoxyuridine- and theophylline-induced changes.

Abstract

ABSTRACT. The relation of the total cellular content of sialic acid to phenotypic expression of B16 mouse melanoma cells was examined by using phenotype-modifying reagents and more than 10 cloned cell lines with spontaneous phenotypic variations. The sialic acid content changed in a growth phase-dependent manner with a peak in the early log phase of growth. This peak completely disappeared when cells were treated with 5-bromodeoxyuridine (BrdU), suggesting its relation to quasi-normal phenotypes of the treated cells. BrdU treatment also reduced the cellular sialic acid content itself and resulted in the suppression of the activity of tyrosinase, the key enzyme for melanogenesis, and a considerable increase in cell-to-substratum adhesiveness. Treatment with theophylline, in contrast, markedly elevated the sialic acid content, which was accompanied by dramatic increments in tyrosinase activity and pigmentation as well as a slight increase in adhesiveness. The results show a correlation of sialic acid level with tyrosinase expression but not with cell adhesion. From comparison of spontaneous phenotypic variations, the correlation of sialic acid level with tyrosinase activity was confirmed, while there was only a slight correlation with adhesiveness. It is thus suggested that sialylation/desialylation, being reflected as variations in cellular sialic acid content, is implicated in melanoma cell differentiation in terms of tyrosinase expression.Sialic acid has been shown to play important roles in a variety of biological processes including cell adhesion, cellular recognition and regulation of glycoconjugates' functions (6,15,19,20,28). In melanoma cells, involvement of sialic acid residues has been well documented in determining metastatic potential (13). A lectin (WGA)-resistant phenotype and the related alteration of adhesive properties have also been shown to be due to a decrease in cell surface sialic acid content (2, 25). However, little has been known of the functional significance of sialic acid relating to other aspects of melanoma cell phenotypes.Treatment of mouse melanoma cells with 5-bromodeoxyuridine (BrdU) (18, 23) or retinoic acid (1) has been shown to result in changes in cellular sialic acid content.

Sequential alteration of peanut agglutinin binding-glycoprotein expression during progression of murine mammary neoplasia

“…However, there is also evidence indicating that in some systems the expression of non-sialylated structures binding SBA (Buckey et al, 1988) or PNA (Badenoch-Jones et al, 1987;Schirrmacher et al, 1982) is associated with metastasis. Sialylation of surface carbohydrates was alternatively correlated with cell proliferation (Kinoshita et al, 1989) or differentiation (Kinoshita et al, 1989;Kuratsu et al, 1990). In some reports only subtle changes in glyconjugate expression patterns were seen between more and less malignant cell lines (Steck & Nicolson, 1983;Tresser & Nicholson, 1988).…”

Effects of CAMP and cGMP Elevating Agents on HL‐60 Cell Differentiation

“…To our knowledge all previous studies on this cell line have been with lower doses (Chaplinski & Niedel 1982;Boss 1989), explaining the relative poor effect on differentiation. Theophylline has previously been shown to increase differentiated characteristics of uveal melanocytes (Hu et al 1987), B-16 melanoma cells (Kinoshita et al 1989), mouse mammary gland (Vanderploeg et al 1992) and Burkitt's lymphoma cell lines (Sandlund et al 1993). The fact that cyclic nucleotide levels were raised after only 30 sec.…”

MRI Visualization of Melanoma Cells by Targeting Overexpressed Sialic Acid with a GdIII‐dota‐en‐pba Imaging Reporter

“…In melanoma cells, the activity of tyrosinase, the key enzyme for melanogenesis, shows a good correlation with intra-and extracellular Sia levels. [10] This indicates an essential role of Sia residues in the enzyme expression and, therefore, in melanoma cells differentiation. Sialylation/desialylation of some relevant molecules, such as melanosomal sialo-glycoconjugates and tyrosinase itself, participate in the regulation of expression of melanogenic functions.…”