Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent.
E-cadherin is a Ca(2+)-dependent cell-cell adhesion molecule, which is mainly expressed in epithelial cells. Recent studies have shown that E-cadherin has an important role as an invasion suppressor molecule in epithelial tumor cells. Syndecan-1 is a cell surface proteoglycan that has been implicated in a number of cellular functions including cell-cell adhesion, cell-matrix anchorage and growth factor presentation for signalling receptors. Its suppression has also been shown to be associated with malignant transformation of epithelial cells. In order to better understand the coordinated regulation of cell-cell and cell-matrix interactions during malignant transformation, we have studied the expression of syndecan-1 in malignant mammary tumor cells genetically manipulated for E-cadherin expression. In invasive NM-e-ras-MAC1 cells, where E-cadherin was partially downregulated by specific antisense RNA, syndecan-1 expression was suppressed. Furthermore, transfection of E-cadherin cDNA into invasive NM-f-ras-TD cells resulted in the upregulation of syndecan-1 expression in association with decreased invasiveness. In both cases, regulation of syndecan-1 occurred post-transcriptionally, since syndecan-1 mRNA levels remained unchanged. Instead, a translational regulation is suggested, since syndecan-1 core protein synthesis was E-cadherin dependent. Another cell adhesion protein, beta 1-integrin was not affected by E-cadherin expression. The data provide an example of coordinated changes in the expression of two cell adhesion molecules, syndecan-1 and E-cadherin during epithelial cell transformation.
Leppä
S
S
Department of Medical Biochemistry, University of Turku, Finland.
Vleminckx
K
K
Van Roy
F
F
Jalkanen
M
M
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D005260:Female; D015870:Gene Expression; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans