Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine).
In many tissues, the TF (Thomsen-Friedenreich) blood group antigen (Galbeta1-3GalNAc alpha-) behaves as an onco-foetal carbohydrate antigen, showing increased expression in malignancy and hyperplasia. Dietary lectins which bind the TF antigen have marked effects on proliferation of epithelial cells without cytotoxicity. This led us to speculate that anti-TF antibodies, including those that naturally occur in humans, might have similar effects. Five anti-TF antibodies, TF2 (human), TF5 (human), 5A8 (mouse), 8D8 (mouse) and BM22 (mouse), but not TFI (human) or 49H.9 (mouse), showed marked dose-dependent stimulation (95-192%) of [3H]thymidine incorporation by HT29 human colon cancer cells. Similar stimulation of proliferation of HT29 cells by these monoclonal antibodies (MAbs) was found when cell count assessment was used. Antibody-stimulated proliferation was inhibited by co-incubation with glycoproteins expressing Galbeta1-3GalNAc alpha- (asialo glycophorin or [Galbeta1-3GalNAc alpha-O-p-aminophenyl]n-human serum albumin). A proliferative effect of these antibodies was also demonstrated on human colon cancer cell lines LS174T and HT29-MTX but not on Caco-2 cells. Although immunoblotting showed similar binding patterns of all the antibodies on HT29 cell membrane extracts, there was little correlation between cell surface binding assessed by immunofluorescence and proliferative response, and internalization of the biotinylated antibody TF5 was demonstrated by confocal microscopy. Our results provide further evidence that cell surface glycoproteins which express TF antigen may play an important role in the regulation of cell proliferation and also suggest that human anti-TF antibodies may have proliferative effects on cells which express TF antigen.
Yu
L G
LG
Department of Medicine, University of Liverpool, UK. lgyu@liv.ac.uk
Jansson
B
B
Fernig
D G
DG
Milton
J D
JD
Smith
J A
JA
Gerasimenko
O V
OV
Jones
M
M
Rhodes
J M
JM
D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004912:Erythrocytes / Q000187:drug effects; D006386:Hemagglutination Tests; D006801:Humans; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; C016467:Thomsen-Friedenreich antigen; C025991:Thomsen-Friedenreich antibodies