Endocrinology, Vol 137, 873-878, Copyright © 1996 by Endocrine Society

ARTICLES

Soluble insulin-like growth factor-II/mannose 6-P receptor inhibits deoxyribonucleic acid synthesis in cultured rat hepatocytes

CD Scott, M Ballesteros, J Madrid and RC Baxter
Royal North Shore Hospital, St. Leonards, New South Wales, Australia.

Insulin-like growth factor-II/mannose 6-P (IGF- II/M6P) receptor is released from cultured cells and tissues in a soluble form that retains its affinity for IGF-II. To test the possibility that soluble receptor can therefore modulate the activity of IGF-II, we determined the effect of purified soluble receptor on DNA synthesis in cultured rat hepatocytes stimulated with epidermal growth factor (EGF) (5 ng/ml) and IGF-II (200 ng/ml). Thymidine incorporation in hepatocytes in the presence of EGF and IGF-II was inhibited by soluble receptor (50% inhibition at 212 +/- 45 ng/ml). However, thymidine incorporation in the presence of EGF alone was also inhibited with similar potency. This inhibitory effect was removed by immunodepletion of receptor from the purified preparation, demonstrating the absence of nonspecific cytotoxic effects of the preparation. Although soluble receptor blocked IGF-II binding to hepatocytes, inhibition of EGF-stimulated DNA synthesis was not due to inhibition of EGF binding or uptake by the cell. These results suggest that soluble IGF-II/M6P receptor not only plays a role in modulating the action of IGF-II but may also have IGF- independent actions on cells, possibly by modulating M6P protein action.

This article has been cited by other articles:

				S. N. Prince, E. J. Foulstone, O. J. Zaccheo, C. Williams, and A. B. Hassan Functional evaluation of novel soluble insulin-like growth factor (IGF)-II-specific ligand traps based on modified domain 11 of the human IGF2 receptor Mol. Cancer Ther., February 1, 2007; 6(2): 607 - 617. [Abstract] [Full Text] [PDF]

				J. Harper, J. L. Burns, E. J. Foulstone, M. Pignatelli, S. Zaina, and A. B. Hassan Soluble IGF2 Receptor Rescues ApcMin/+ Intestinal Adenoma Progression Induced by Igf2 Loss of Imprinting Cancer Res., February 15, 2006; 66(4): 1940 - 1948. [Abstract] [Full Text] [PDF]

				A. B. Hassan Keys to the Hidden Treasures of the Mannose 6-Phosphate/Insulin-Like Growth Factor 2 Receptor Am. J. Pathol., January 1, 2003; 162(1): 3 - 6. [Full Text] [PDF]

				D. B. O'Gorman, J. Weiss, A. Hettiaratchi, S. M. Firth, and C. D. Scott Insulin-Like Growth Factor-II/Mannose 6-Phosphate Receptor Overexpression Reduces Growth of Choriocarcinoma Cells in Vitro and in Vivo Endocrinology, November 1, 2002; 143(11): 4287 - 4294. [Abstract] [Full Text] [PDF]

				K. Ong, J. Kratzsch, W. Kiess, M. Costello, C. Scott, and D. Dunger Size at Birth and Cord Blood Levels of Insulin, Insulin-Like Growth Factor I (IGF-I), IGF-II, IGF-Binding Protein-1 (IGFBP-1), IGFBP-3, and the Soluble IGF-II/Mannose-6-Phosphate Receptor in Term Human Infants J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4266 - 4269. [Abstract] [Full Text]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]

				M. Costello, R. C. Baxter, and C. D. Scott Regulation of Soluble Insulin-Like Growth Factor II/Mannose 6-Phosphate Receptor in Human Serum: Measurement by Enzyme-Linked Immunosorbent Assay J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 611 - 617. [Abstract] [Full Text]

				S. Zaina and S. Squire The Soluble Type 2 Insulin-like Growth Factor (IGF-II) Receptor Reduces Organ Size by IGF-II-mediated and IGF-II-independent Mechanisms J. Biol. Chem., October 30, 1998; 273(44): 28610 - 28616. [Abstract] [Full Text] [PDF]

				S. Zaina, R. V. S. Newton, M. R. Paul, and C. F. Graham Local Reduction of Organ Size in Transgenic Mice Expressing a Soluble Insulin-Like Growth Factor II/Mannose-6-Phosphate Receptor Endocrinology, September 1, 1998; 139(9): 3886 - 3895. [Abstract] [Full Text] [PDF]