Fibronectin receptor overexpression and loss of transformed phenotype in a stable variant of the K562 cell line.
A variant of the K562 erythroleukemia cell line, FA-K562, was selected by cycles of adhesion to solid-phase plasma fibronectin (FN). FA-K562 expresses fourfold more cell-surface alpha 5 beta 1 fibronectin receptor (FNR) than parental K562. In addition to expected differences in adhesion to FN, other differences between FA-K562 and K562 implicate this FNR in the regulation of cell growth and morphology. FA-K562 proliferates slowly in liquid culture, its cloning efficiency in soft agar is only approximately 10% compared with approximately 85% for parental K562, and it is nontumorigenic in nude mice. The reduced soft agar growth potential of FA-K562 involves FNR function, because either glycine-arginine-glycine-aspartate-serine (GRGDS) or monoclonal anti-alpha 5 antibody in the agar medium increased cloning efficiency of FA-K562 about fivefold. Morphologically, FN-adherent FA-K562 become fibroblastoid in appearance, assemble filamentous actin, and differ from K562 in vimentin staining intensity and pattern. Soluble GRGDS peptide inhibits both FA-K562 adhesion to FN and the associated cytoskeletal changes. These findings link the alpha 5 beta 1 FNR to both the transformed phenotype and morphology of FA-K562.
Symington
B E
BE
Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, Washington 98104.
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003599:Cytoskeleton; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010641:Phenotype; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D005353:Fibronectins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D014746:Vimentin