This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pommier, G. J. Articles by Remacle-Bonnet, M. M. Search for Related Content PubMed PubMed Citation Articles by Pommier, G. J. Articles by Remacle-Bonnet, M. M.

Potential Autocrine Role of Insulin-like Growth Factor II during Suramin-induced Differentiation of HT29-D4 Human Colonic Adenocarcinoma Cell Line¹

Laboratoire d'Immunopathologie, Faculté de Médecine [G. J. P., F. L. G., F. E. A.], and Institut de Chimie Biologique, CNRS-URA 202, Faculté des Sciences [M. R., J. L. M., M. M. R. B.], Marseille, France

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 mM 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 ¹²⁵I-IGF-II-IGFBP complexes. However, the addition of 40–100 µg/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 µg/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 µg/ml) or agonist monoclonal antibody IR-3 (2.5 µg/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.

¹ Supported by grants from the Association pour la Recherche sur le Cancer and Ligue Nationale Française contre le Cancer.

² To whom requests for reprints should be addressed, at Laboratoire d'Immunopathologie, Faculté de Médecine, 27, Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.

Received 11/ 5/91. Accepted 3/20/92.

This article has been cited by other articles:

				E. J. Kim, I.-J. Kang, H. J. Cho, W. K. Kim, Y.-L. Ha, and J. H. Y. Park Conjugated Linoleic Acid Downregulates Insulin-Like Growth Factor-I Receptor Levels in HT-29 Human Colon Cancer Cells J. Nutr., August 1, 2003; 133(8): 2675 - 2681. [Abstract] [Full Text] [PDF]

				H. Cui, M. Cruz-Correa, F. M. Giardiello, D. F. Hutcheon, D. R. Kafonek, S. Brandenburg, Y. Wu, X. He, N. R. Powe, and A. P. Feinberg Loss of IGF2 Imprinting: A Potential Marker of Colorectal Cancer Risk Science, March 14, 2003; 299(5613): 1753 - 1755. [Abstract] [Full Text] [PDF]

				L. Shalamanova, B. Kubler, J.-G. Scharf, and T. Braulke MDCK cells secrete neutral proteases cleaving insulin-like growth factor-binding protein-2 to -6 Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1221 - E1229. [Abstract] [Full Text] [PDF]

				M. Lehmann, F. Andre, C. Bellan, M. Remacle-Bonnet, F. Garrouste, F. Parat, J.-C. Lissitsky, J. Marvaldi, and G. Pommier Deficient Processing and Activity of Type I Insulin-Like Growth Factor Receptor in the Furin-Deficient LoVo-C5 Cells Endocrinology, September 1, 1998; 139(9): 3763 - 3771. [Abstract] [Full Text] [PDF]

				F. L. Garrouste, M. M. Remacle-Bonnet, M. M.-A. Lehmann, J. L. Marvaldi, and G. J. Pommier Up-Regulation of Insulin/Insulin-Like Growth Factor-I Hybrid Receptors during Differentiation of HT29-D4 Human Colonic Carcinoma Cells Endocrinology, May 1, 1997; 138(5): 2021 - 2032. [Abstract] [Full Text] [PDF]