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 gro...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1992-06, Vol.52 (11), p.3182-3188
Main Authors: POMMIER, GJ, GARROUSTE, FL, ELATIQ, F, ROCCABIANCA, M, MARVALDI, JL, REMACLEBONNET, MM
Format: Article
Language:English
Subjects:
Adenocarcinoma - ultrastructure
Antineoplastic agents
Biological and medical sciences
Carcinoembryonic Antigen - analysis
Carrier Proteins - metabolism
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Line
Colonic Neoplasms - ultrastructure
General aspects
Humans
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor II - metabolism
Insulin-Like Growth Factor II - physiology
Kinetics
Life Sciences & Biomedicine
Medical sciences
Microscopy, Electron
Oncology
Pharmacology. Drug treatments
Science & Technology
Suramin - pharmacology
Tumor Cells, Cultured
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Summary: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 (K(da) = 0.02 nM and K(db) = 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 I-125-IGF-II-IGFBP complexes. However, the addition of 40-100-mu-g/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-mu-g/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-mu-g/ml) or agonist monoclonal antibody alpha-IR-3 (2.5-mu-g/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.
ISSN:0008-5472
1538-7445