Endocrinology, Vol 126, 3033-3042, Copyright © 1990 by Endocrine Society

ARTICLES

Autocrine regulation of human tumor cell proliferation by insulin-like growth factor II: an in-vitro model

MA Thompson, AJ Cox, RH Whitehead and HA Jonas
University of Melbourne Department of Medicine, Victoria, Australia.

We have shown that a pleomorphic cell line of abnormal human karyotype derived from a stomach carcinoma (LIM-1839) proliferates in serum-free medium, expresses insulin-like growth factor II (IGF-II) mRNA, and secretes IGF-II (up to 56 ng/ml in serum-free conditioned medium, as measured in a rat liver RRA. No detectable levels of IGF-I can be measured in serum-free conditioned medium by RIA. These cells also secrete IGF-binding proteins, detected by a charcoal adsorption assay. The release of IGF-II and IGF binding proteins into serum-free conditioned medium (1.7 pmol/10(6) cells.24 h and 0.8 pmol binding sites/10(6) cells.24 h for 3 days, respectively) is inhibited 80% by cycloheximide (10 micrograms/ml). The LIM-1839 cells have type I and type II IGF receptors, determined by affinity cross-linking and competition binding studies. These cells proliferated 1.6-fold over 4 days in serum-free medium, with fresh medium changes on days 0 and 2: their growth was inhibited 56% by 40 micrograms/ml Sm 1.2, a monoclonal antibody which recognizes IGF-I and IGF-II. The addition of 20 and 50 ng/ml multiplication stimulating activity (rat IGF-II) caused 1.8- and 1.7-fold increases in cell growth between days 0 and 4 compared to controls, while [Thr59]IGF-I, at 20 and 50 ng/ml, caused 1.6- and 2.0- fold increases. Insulin, at 2 and 10 micrograms/ml, had no significant effect. The stimulatory effects of endogenous and exogenous IGFs on LIM- 1839 cell proliferation were inhibited by a monoclonal antibody to the type I IGF receptor, alpha IR-3. These results suggest that the LIM- 1839 cells are biologically responsive to endogenously produced IGF-II, and may thereby provide an in vitro model for autocrine regulation of human tumor growth by IGF-II.

This article has been cited by other articles:

				W. Piao, Y. Wang, Y. Adachi, H. Yamamoto, R. Li, A. Imsumran, H. Li, T. Maehata, M. Ii, Y. Arimura, et al. Insulin-like growth factor-I receptor blockade by a specific tyrosine kinase inhibitor for human gastrointestinal carcinomas Mol. Cancer Ther., June 1, 2008; 7(6): 1483 - 1493. [Abstract] [Full Text] [PDF]

				G. Sonvilla, S. Allerstorfer, S. Stattner, J. Karner, M. Klimpfinger, H. Fischer, B. Grasl-Kraupp, K. Holzmann, W. Berger, F. Wrba, et al. FGF18 in colorectal tumour cells: autocrine and paracrine effects Carcinogenesis, January 1, 2008; 29(1): 15 - 24. [Abstract] [Full Text] [PDF]

				L. Lu, D. Katsaros, A. Wiley, I. A. Rigault de la Longrais, H. A. Risch, M. Puopolo, and H. Yu The Relationship of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor Binding Protein-3, and Estrogen Receptor-{alpha} Expression to Disease Progression in Epithelial Ovarian Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1208 - 1214. [Abstract] [Full Text] [PDF]

				Y Min, Y Adachi, H Yamamoto, A Imsumran, Y Arimura, T Endo, Y Hinoda, C-T Lee, S Nadaf, D P Carbone, et al. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts Gut, May 1, 2005; 54(5): 591 - 600. [Abstract] [Full Text] [PDF]

				D. Iwakiri, Y. Eizuru, M. Tokunaga, and K. Takada Autocrine Growth of Epstein-Barr Virus-Positive Gastric Carcinoma Cells Mediated by an Epstein-Barr Virus-Encoded Small RNA Cancer Res., November 1, 2003; 63(21): 7062 - 7067. [Abstract] [Full Text] [PDF]

				H. M. Khandwala, I. E. McCutcheon, A. Flyvbjerg, and K. E. Friend The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth Endocr. Rev., June 1, 2000; 21(3): 215 - 244. [Abstract] [Full Text]