Episialin (MUC1, PEM, EMA, CA15-3 antigen) is a sialylated, membrane-associated glycoprotein with an extended mucin-like ectodomain. This domain mainly consists of 30-90 homologous 20-amino acid repeats that are rich in O-glycosylation sites (serines and threonines). It is likely that this part forms a polyproline beta-turn helix. As a result, the ectodomain can protrude more than 200 nm above the cell surface, whereas most cell surface molecules do not exceed a length of 35 nm. Normally, episialin is present at the apical side of glandular epithelial cells. On carcinoma cells, however, it can be strongly overexpressed and it is often present over the entire cell surface. We have previously shown that episialin, if it is interspersed between adhesion molecules, nonspecifically reduces cell-cell and cell-extracellular matrix interactions in vitro and in vivo, presumably by steric hindrance caused by the extreme length and high density of the episialin molecules at the cell surface. To analyze the molecular mechanism for this anti-adhesion effect in more detail, we have now deleted an increasing number of repeats in the episialin cDNA and transfected the resulting mutants into murine L929 cells expressing the homophilic adhesion molecule E-cadherin. Here we show that the length of episialin is the dominant factor that determines the inhibition of E-cadherin-mediated cell-cell interactions. For the anti-adhesive effect mediated by the full length episialin, charge repulsion by negatively charged sialylated O-linked glycans is far less important.

Conference Article| November 01 1995 Involvement of the cell surface-bound mucin, episialin/MUCI, in progression of human carcinomas J. Hilkens; J. Hilkens 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar J. Wesseling; J. Wesseling 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar H. L. Vos; H. L. Vos 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar J. Storm; J. Storm 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar B. Boer; B. Boer 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar S. W. van der Valk; S. W. van der Valk 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar M. C. E. Maas M. C. E. Maas 1Division of Tumour Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), 1066 CX Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (4): 822–826. https://doi.org/10.1042/bst0230822 Article history Received: June 22 1995 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation J. Hilkens, J. Wesseling, H. L. Vos, J. Storm, B. Boer, S. W. van der Valk, M. C. E. Maas; Involvement of the cell surface-bound mucin, episialin/MUCI, in progression of human carcinomas. Biochem Soc Trans 1 November 1995; 23 (4): 822–826. doi: https://doi.org/10.1042/bst0230822 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.

Episialin (MUC1) is a transmembrane molecule with a large mucin-like extracellular domain protruding high above the cell surface. The molecule is located at the apical side of most glandular epithelial cells, whereas in carcinoma cells it is often present at the entire surface and it is frequently expressed in abnormally large quantities. We have previously shown that overexpression of episialin reduces cell- cell interactions. Here we show that the integrin-mediated adhesion to extracellular matrix of transfectants of a melanoma cell line (A375), a transformed epithelial cell line (MDCK-ras-e) and a human breast epithelial cell line (HBL-100) is reduced by high levels of episialin. This reduction can be reversed by inducing high avidity of the beta 1 integrins by mAb TS2/16 (at least for beta 1-mediated adhesion). The adhesion can also be restored by redistribution of episialin on the cell surface by monoclonal antibodies into patches or caps. Similarly, capping of episialin on ZR-75-1 breast carcinoma cells, growing in suspension, caused adherence and spreading of these cells. We propose that there is a delicate balance between adhesion and anti-adhesion forces in episialin expressing cells, which can be shifted towards adhesion by strengthening the integrin-mediated adhesion, or towards anti-adhesion by increasing the level of expression of episialin.