The effects of insulin-like growth factor binding protein-3 (IGFBP-3) on T47D breast cancer cells enriched for IGFBP-3 binding sites.
To investigate insulin-like growth factor (IGF)-independent effects of IGF binding protein-3 (IGFBP-3), T47D cells were enriched for a population of cells that expressed binding sites for biotinylated-IGFBP-3 by panning on streptavidin-coated plate. Proliferation of cell enriched for IGFBP-3 binding sites was significantly inhibited by IGFBP-3, whereas IGFBP-3 had no significant effect on the non-enriched cell population. Enriched and non-enriched cells were equally responsive to IGF-I, TGF-beta and EGF. Conditioned medium from enriched cells had less IGFBP-3 than that from non-enriched cells. Cross-linking of biotinylated IGFBP-3 to T47D cell membranes identified complexes with Mr of 32, 80 and 100 kDa. All of these complexes were more abundant in enriched cells compared with the non-enriched cell population. These data demonstrate that despite the anti-proliferative effects of IGFBP-3 it is possible to selectively enriched for cell populations with more abundant IGFBP-3 binding sites. These enriched cells are more responsive to IGFBP-3 and secrete less of this binding protein than non-enriched cells, supporting the concept that IGFBP-3 secretion by human breast cancer cells may function as an autocrine or paracrine modulator of cell proliferation.
Mishra
Suresh
S
Departments of Internal Medicine & Physiology, University of Manitoba, Winnipeg R3E 0W3 Canada.
Murphy
Liam J
LJ
D017209:Apoptosis; D001665:Binding Sites; D019921:Biotinylation; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000032:analysis; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors
D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3