Document Detail

Insulin like growth factor I is an autocrine regulator of human colon cancer cell differentiation and growth.
MedLine Citation:
PMID:  1311629     Owner:  NLM     Status:  MEDLINE    
The polyanionic compound suramin triggers enterocyte-like differentiation of the human colic adenocarcinoma cell clone HT29-D4. We now demonstrate that suramin interferes with the binding of IGF-I to its receptor at the surface of HT29-D4 cells. Half-maximum inhibition of 125I-IGF-I binding was obtained in the presence of 25 micrograms/ml suramin. Moreover, the drug was able to dissociate 125I-IGF previously bound to its cell surface receptor. Affinity labeling HT29-D4 cells were cultured in the presence of 10 micrograms/ml of alpha-IR3, a monoclonal antibody directed against the binding site of IGF-I, an inhibition of cell proliferation and a stimulation of cell differentiation was observed. After 10 days of treatment with alpha-IR3, HT29-D4 cells formed a regular monolayer of enterocyte-like cells exhibiting an apical brush border and tight junctions delimiting two domains of the plasma membrane (apical and basolateral). Furthermore, we show that IGF-I significantly increased the initial rate of glucose uptake by HT29-D4 cells, while we have previously shown that suramin decreased glucose consumption. From these data we conclude that IGF-I secreted by the cells themselves, stimulates proliferation of HT29-D4 cells via an autocrine mechanism. Blockade of this stimulation by suramin or by a specific monoclonal antibody inhibits cell growth, glucose uptake and triggers the process of enterocytic differentiation.
S Baghdiguian; B Verrier; C Gerard; J Fantini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  62     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  1992 Feb 
Date Detail:
Created Date:  1992-04-06     Completed Date:  1992-04-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  23-33     Citation Subset:  IM    
INSERM U270, Faculté de Médecine, Marseille, France.
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MeSH Terms
Biological Transport / drug effects
Cell Differentiation / drug effects
Cell Division / drug effects
Cell Polarity
Colonic Neoplasms / pathology*
Fluorescent Antibody Technique
Glucose / metabolism
Insulin-Like Growth Factor I / pharmacology,  physiology*
Receptors, Cell Surface / physiology*
Receptors, Somatomedin
Suramin / pharmacology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Receptors, Cell Surface; 0/Receptors, Somatomedin; 145-63-1/Suramin; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I

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