Potential autocrine role of insulin-like growth factor II during suramin-induced differentiation of HT29-D4 human colonic adenocarcinoma cell line.
Suramin, a drug that binds to several types of growth factors, has been previously shown to induce the enterocyte-like differentiation of HT29-D4 human colonic adenocarcinoma cells, suggesting that growth factors are involved in such a process. Undifferentiated HT29-D4 cells release insulin-like growth factor II (IGF-II) into the culture medium that is totally complexed to heterogeneous IGF binding proteins (IGFBP) expressing high affinities for this growth factor (Kda = 0.02 nM and Kdb = 1.4 nM). These complexes do not allow IGF-II to bind to HT29-D4 cell surface type I IGF receptors, as evidenced by using 125I-IGF-II-IGFBP complexes. However, the addition of 40-100 micrograms/ml suramin, i.e., concentrations identical to the ones that are able to induce HT29-D4 cell differentiation, induces the release of IGF-II from IGF-II-IGFBP complexes, thereby allowing IGF-II to bind to the cell surface receptors. At such concentrations, suramin is indeed unable to alter IGF-II binding to HT29-D4 cells, a capacity that is observed only for concentrations higher than 200 micrograms/ml. Thus, suramin might have the unusual capacity to allow the establishment of an IGF-II autocrine loop involved in HT29-D4 cell differentiation. Consistent with this hypothesis is the fact that exogenously applied IGF-I (2.5 micrograms/ml) or agonist monoclonal antibody alpha IR-3 (2.5 micrograms/ml), which can bypass IGFBP present in the culture medium, induces part of HT29-D4 cell differentiation that is characterized by an important carcinoembryonic antigen release and the induction of numerous intercellular cysts with microvilli.
Pommier
G J
GJ
Laboratoire d'Immunopathologie, Faculté de Médecine, CNRS-URA 202, Marseille, France.
Garrouste
F L
FL
el Atiq
F
F
Roccabianca
M
M
Marvaldi
J L
JL
Remacle-Bonnet
M M
MM
D000230:Adenocarcinoma / Q000648:ultrastructure; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000648:ultrastructure; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008854:Microscopy, Electron; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D013498:Suramin; D007335:Insulin-Like Growth Factor II