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.
Int J Cancer
; 58(3): 452-9, 1994 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-8050827
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor II del Crecimiento Similar a la Insulina
/
Neoplasias Colorrectales
/
Receptor IGF Tipo 1
/
Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Revista:
Int J Cancer
Año:
1994
Tipo del documento:
Article
Pais de publicación:
Estados Unidos