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

✍ Scribed by Harald Lahm; Paul Amstad; Josiane Wyniger; Aysim Yilmaz; Jürgen R. Fischer; Magali Schreyer; Jean-Claude Givel

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 930 KB
• Volume: 58
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910580325

✦ Synopsis

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 I2/ I 2 colorectal carcinoma cell lines tested. alR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/ I 2 lines (Caco-2, HT-29, LS41 IN, LS5 13, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (I9 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, LS5 13, LS 1034, WiDr) alR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized culR3mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-ll transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-ll-mediated stimulation of the IGF-I-R.