Increased glycosylation of beta 1 integrins affects the interaction of transformed S115 mammary epithelial cells with laminin-1.
The effect of transformation on the expression and the functions of beta 1 integrins was studied using an in vitro cell transformation model. S115 mammary epithelial tumor cells undergo transformation into tumorigenic fibroblastoid cells in the presence of steroids. Transformation was found to reduce the attachment and the spreading of S115 cells on laminin-1 but not fibronectin. Adhesion of S115 cells to laminin-1 was inhibited in the presence of an antibody against the beta 1 integrin subunit. Both nontreated and transformed S115 cells expressed at least two putative laminin-1-binding beta 1 integrins at the same level. In transformed cells, however, the mature integrin subunits appeared to be structurally altered, showing a slower electrophoretic mobility. Treatment with N-glycosidase-F and tunicamycin abolished this mobility difference, suggesting that the presence of complex-type N-linked oligosaccharides was responsible. Detailed enzymatic analysis of the oligosaccharides present on the beta 1 subunits revealed that the difference in glycosylation is, at least partially, due to poly-N-lactosaminoglycan chains on beta 1 integrin from transformed cells. Removal of this difference in glycosylation by either cleavage of the polylactosaminoglycan chains with endo-beta-galactosidase or inhibiton of complex-type glycan formation with swainsonine repeatedly enhanced the spreading of transformed cells on laminin-1. Thus, the increased size of complex-type oligosaccharides on beta 1 integrin may affect cell-laminin-1 interactions. Similar changes may contribute to the altered adhesion of cancer cells during the invasion and metastasis.
Leppä
S
S
Department of Medical Biochemistry, University of Turku, Finland.
Heino
J
J
Jalkanen
M
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004847:Epithelial Cells; D006031:Glycosylation; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008970:Molecular Weight; D011134:Polysaccharides / Q000037:antagonists & inhibitors; D013739:Testosterone / Q000494:pharmacology
D019012:Integrin beta1; D007797:Laminin; D011134:Polysaccharides; D013739:Testosterone