Transcobalamin II and in vitro proliferation of leukemic cells.
We have recently shown that antibodies to transcobalamin II (TCII) inhibit the in vitro growth of human and murine leukemic cells. This antiproliferative strategy targets the uptake of cobalamin (Cbl), an essential cofactor for two biochemical reactions in humans. To date there has been no appropriate cell culture model available to study antagonism of Cbl as a potential antiproliferative strategy. We have established cell culture conditions which allow reproducible measurements of cell proliferation that is dependent on Cbl and its carrier protein, TCII. This bioassay has allowed us to demonstrate that several monoclonal antibodies, raised against TCII, are potent inhibitors of cell proliferation and that excess Cbl abrogates this inhibitory effect. Thus, supporting our hypothesis that interference with Cbl uptake or metabolism will result in inhibition of cell proliferation. Furthermore, Cbl metabolism appears to provide a useful target for antiproliferative strategies which now involve the use of inactive Cbl analogs. In this review, we update our work on the role of targeting TCII and Cbl as an antiproliferative strategy for leukemic cells. We suggest that this strategy may provide a novel direction for anti cancer reagents.
McLean
G R
GR
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Williams
M J
MJ
Woodhouse
C S
CS
Ziltener
H J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001681:Biological Assay; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology*; D014155:Transcobalamins / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D014155:Transcobalamins