The mucin epiglycanin on TA3/Ha carcinoma cells prevents alpha 6 beta 4-mediated adhesion to laminin and kalinin and E-cadherin-mediated cell-cell interaction.

Abstract

Abstract. TA3/Ha murine mammary carcinoma cells grow in suspension, do not adhere to extracellular matrix molecules, but do adhere to hepatocytes and form liver metastases upon intraportal injection. Recently we showed that the integrin ottfl4 on the TA3/Ha cells is involved in adhesion to hepatocytes. However, despite high cell surface levels of o~6B4, TA3/Ha cells do not adhere to the ot6~4 ligands laminin and kalinin. Here we show that this is due to the mucin epiglycanin that is highly expressed on TA3/Ha cells. Some monoclonal antibodies generated against epiglycanin induced capping of most of the epiglycanin molecules. TA3/Ha cells treated with these mAb did adhere to laminin and kalinin, and an epithelial monolayer was formed on kalinin, with ot6~4 localized in HDl-containing hemidesmosome-like structures and E-cadherin at the cell-cell contact sites. Similar results were obtained after treatment of TA3/Ha cells with O-sialoglycoprotein endopeptidase which removes all epiglycanin. In addition, the enzyme induced E-cadherin-mediated cell-cell aggregation. Both treatments also enhanced the adhesion to hepatocytes, but given the potent antiadhesive effect of epiglycanin it is remarkable that nontreated TA3/Ha cells adhere to hepatocytes at all. We found that during this interaction, epiglycanin was redistributed. We conclude that epiglycanin can completely prevent both intercellular and matrix adhesion, but that this effect can be overcome in certain intercellular interactions because of the induced redistribution of the mucin.

Enhanced podocalyxin expression alters the structure of podocyte basal surface

“…It has been proposed that mucins interfere with cell-cell or cell-matrix adhesion either through steric hindrance, by masking adhesion molecules and/or by charge repulsion Kemperman et al, 1994;Wesseling et al, 1995;Takeda et al, 2000). In the present report, we provide evidence that in addition to charge repulsion, antiadhesive properties of PC may compete with β1 integrinmediated adhesion.…”

“…Antiadhesive effects have also been demonstrated for other mucins such as episialin, epiglycanin, and leukosialin. The antiadhesive properties of mucins were often revealed by the use of antibodies directed against their extracellular domain (protein core) Cyster and Williams, 1992;DeSmet et al, 1993;Kemperman et al, 1994;Wesseling et al, 1995). Cyster and Williams (1992) suggested that monoclonal antibodies, which recognize the protein core of mucin leukosialin, overcame the repulsion created by the negative charges of this sialoprotein, thus allowing other adhesion molecules to come into play inducing cell-cell interactions.…”

Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

“…For example, epiglycanin, which is highly expressed on the TA3/Ha mouse mammary tumor cell line, inhibits E-cadherin and integrinmediated adhesion (Kemperman et al, 1994). Similarly, ectopic expression of episialin in adherent cell lines also inhibits E-cadherin and integrin-mediated adhesion (Wesseling et al, 1995(Wesseling et al, , 1996.…”

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

“…For example, epiglycanin, which is expressed at high levels by the mouse mammary tumor cell line TA3/Ha, also inhibits E-cadherin and integrin-mediated adhesion (Kemperman et al, 1994). The expression of yet another sialomucin, the hematopoietic stem cell marker CD34, is reciprocally regulated with the expression of adhesion molecules on endothelium (Delia et al, 1993).…”