Tumour cells which develop resistance to cytolysis by tumour necrosis factor have a different glycoform of a 105-kDa glycoprotein and lose the capacity to invade and metastasize.
A plastic-adherent variant of human myelomonocytic leukaemia cells (U937) is highly susceptible to direct TNF cytolysis in vitro. Previously, we found that a subline selected for resistance to TNF cytolysis (U937/R) was much less motile and more plastic-adherent than the parental line. In the present study we show that U937 and U937/R cells have different glycoforms of a 105-kDa cell-surface glycoprotein. This protein is predominantly N-glycosylated and has the physicochemical properties of the LAMP-I glycoprotein. In nude mice, U937 cells are highly malignant whereas U937/R cells form a benign, encapsulated tumour. Therefore, possession of a different glycoform of the 105-kDa glycoprotein by U937/R cells correlates not only with loss of TNF susceptibility but also with reduced invasiveness and metastasis.
Neale
M L
ML
Department of Medical Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Fiera
R A
RA
Matthews
N
N
D002460:Cell Line / Q000032:analysis / Q000187:drug effects / Q000473:pathology; D004351:Drug Resistance; D006023:Glycoproteins / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism / Q000473:pathology*; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D006023:Glycoproteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha