Differences in the biosynthesis and localization of the fibronectin receptor in normal and transformed cultured human cells.
We examined the biosynthesis and localization of the fibronectin receptor integrin from normal and transformed cultured human cells. Normal cells required a minimum of 20 h for the biosynthesis of completely mature fibronectin-receptor beta-subunit, while transformed cells required only 6-8 h. There was a correspondingly major decrease in the amount of the intracellular beta-chain precursor in the transformants. Immunostaining of normal fibroblastic cells with monoclonal antibodies indicated that both alpha- and beta-polypeptides of the fibronectin receptor are localized in cell surface streaks and focal contact areas. In contrast, both subunits lacked this clustering and had a more diffuse distribution on the surfaces of transformed cells, even though quantitative immunofluorescence experiments indicated that similar or larger amounts of each subunit were present on a per cell basis. Both immunostaining and biochemical analyses also indicated the presence of a relatively large intracellular pool of beta-polypeptides in normal fibroblasts that is not present in transformed cells. There was no major transformation-dependent change in total quantities of mature fibronectin receptor subunit expressed and inserted into the plasma membrane, when normalized to total protein synthesis. Our results indicate that malignant transformation of cultured human cells results in altered localization and processing of the fibronectin receptor. Such changes involving pathways of crucial cell surface molecules may contribute to alterations in their interactions with extracellular macromolecules, including during the process of cellular invasion.
Akiyama
S K
SK
Department of Biochemistry, Howard University College of Medicine, Washington, DC 20060.
Larjava
H
H
Yamada
K M
KM
D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D005353:Fibronectins; D016023:Integrins