Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop

Détails

ID Serval
serval:BIB_8D56B9B085AB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop
Périodique
International Journal of Cancer
Auteur(s)
Lahm  H., Amstad  P., Wyniger  J., Yilmaz  A., Fischer  J. R., Schreyer  M., Givel  J. C.
ISSN
0020-7136 (Print)
Statut éditorial
Publié
Date de publication
08/1994
Volume
58
Numéro
3
Pages
452-9
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Résumé
Insulin-like growth factors (IGFs) are potent proliferation stimulators for numerous tumor cells and often function as autocrine growth factors. We have previously shown that exogenous IGF-I and IGF-II enhance proliferation of colorectal carcinoma cells. The biological signal of both factors is transmitted through the IGF-I receptor (IGF-I-R). This receptor was expressed in 12/12 colorectal carcinoma cell lines tested. alpha IR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/12 lines (Caco-2, HT-29, LS411N, LS513, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (19 to 42%), a decrease in cell number (39 to 72%) and an increase in doubling time (up to 2-fold). In addition, in 4 cell lines (Caco-2, LS513, LS1034, WiDr) alpha IR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized alpha IR3-mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-II transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alpha IR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-II-mediated stimulation of the IGF-I-R.
Mots-clé
Antibodies, Monoclonal/*pharmacology Blotting, Northern Cell Adhesion Cell Division/drug effects/physiology Colorectal Neoplasms/*pathology/*ultrastructure Culture Media Humans Insulin-Like Growth Factor I/biosynthesis/pharmacology Insulin-Like Growth Factor II/biosynthesis/*physiology Methylcellulose Receptor, IGF Type 1/*antagonists & inhibitors/immunology Tumor Cells, Cultured Tumor Stem Cells/drug effects
Pubmed
Web of science
Création de la notice
28/01/2008 9:56
Dernière modification de la notice
20/08/2019 15:51
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