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
| Autor: | Harald Lahm, Josiane Wyniger, Jean-Claude Givel, Jürgen Fischer, Magali Schreyer, Aysim Yilmaz, Paul Amstad |
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| Rok vydání: | 1994 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.medical_treatment Methylcellulose Biology Receptor IGF Type 1 chemistry.chemical_compound Insulin-Like Growth Factor II Cell surface receptor Internal medicine Cell Adhesion Tumor Cells Cultured medicine Humans Insulin-Like Growth Factor I Autocrine signalling Cell growth Growth factor Antibodies Monoclonal Blotting Northern Culture Media Endocrinology Cytokine Oncology chemistry Cell culture Insulin-like growth factor 2 Neoplastic Stem Cells Cancer research biology.protein Growth inhibition Colorectal Neoplasms Cell Division |
| Zdroj: | International Journal of Cancer. 58:452-459 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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