Transforming growth factor-beta switches the pattern of integrins expressed in MG-63 human osteosarcoma cells and causes a selective loss of cell adhesion to laminin.
Transforming growth factor-beta (TGF-beta) induces a marked decrease in adhesion of MG-63 human osteosarcoma cells to laminin-coated surfaces, but does not significantly alter adhesion to fibronectin- or collagen-coated surfaces. We provide evidence that this effect is due to a switch in the repertoire of cell adhesion receptors in response to TGF-beta. MG-63 cells express high levels of alpha 3 beta 1-integrin, which is a polyspecific laminin/collagen/fibronectin receptor, and low levels of alpha 2 beta 1- and alpha 5 beta 1-integrins, which are collagen and fibronectin receptors, respectively. No other integrins of the beta 1-class could be detected in MG-63 cells. Treatment with TGF-beta 1 induces a marked (approximately 60%) decrease in the level of expression of alpha 3-integrin subunit mRNA and protein and a concomitant 8-fold increase in alpha 2-subunit expression. These responses become maximal 7-12 h after addition of TGF-beta 1 to the cells. Expression of alpha 5- and beta 1-integrin subunits also increases in response to TGF-beta 1, but to a lesser extent than alpha 2-subunit expression. Thus, as a result of TGF-beta action, the alpha 2 beta 1-collagen and alpha 5 beta 1-fibronectin receptors replace the alpha 3 beta 1-laminin/collagen/fibronectin receptor as the predominant integrins of the beta 1-class in MG-63 cells. These results suggest that one of the effects of TGF-beta is to modify the adhesive behavior of certain tumor cells by changing the binding specificity of the complement of integrins that they express.
Heino
J
J
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
Massagué
J
J
D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D005796:Genes / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D007797:Laminin / Q000378:metabolism*; D046911:Macromolecular Substances; D012516:Osteosarcoma; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D003094:Collagen