Development of tumor cell resistance to tumor necrosis factor cytolysis results in reduced fibronectin binding and altered ganglioside expression.
U937A cells are highly susceptible to tumor necrosis factor (TNF) cytolysis. They are also motile and incorporate fibronectin into the extracellular matrix (ECM). This takes the form of a dense fibrillar network in confluent cultures, but in sparse cultures appears as a "snail trail" of insolubilized fibronectin behind the moving cell. In contrast, U937A/R cells selected for resistance to TNF cytolysis are poorly motile and, although they synthesize fibronectin, fail to incorporate it into the ECM. Compared to U937A/R, U937A cells spread more rapidly and extensively on fibronectin-coated plastic and also bound 125I-fibronectin more effectively. Inhibition of U937A spreading on fibronectin required higher doses of GRGDSPK peptide, indicating greater expression on U937A of integrin-type, fibronectin receptors. Gangliosides are non-integrin structures which can bind fibronectin, and there were also qualitative and quantitative differences in ganglioside expression with U937A having two to five times more than U937A/R. Therefore the development of TNF resistance by U937A/R cells is accompanied by a reduced ability to interact with fibronectin, and this probably accounts for the reduced motility and inability to deposit fibronectin in the ECM.
Dept. Medical Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
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ML
Neale
K M
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Taylor
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Matthews
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D016403:Lymphoma, Large B-Cell, Diffuse; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005353:Fibronectins; D005732:Gangliosides; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D011503:Transglutaminases