Endocrinology, Vol 131, 1703-1710, Copyright © 1992 by Endocrine Society

ARTICLES

Insulin-like growth factor-I (IGF-I) and transforming growth factor- beta 1 release IGF-binding protein-3 from human fibroblasts by different mechanisms

JL Martin, M Ballesteros and RC Baxter
Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Human neonatal fibroblasts in monolayer culture secrete insulin-like growth factor-binding proteins (IGFBPs), which may modulate IGF action. To examine whether an increase in extracellular concentrations of IGFBPs in response to IGF-I is due to the release of cell-associated IGFBPs, we measured secreted and cell-associated IGFBP-3 immunologically in fibroblast monolayers treated with IGF-I and IGF analogs with altered affinities for the IGF receptors and IGFBPs. IGFBP- 3 in medium conditioned by fibroblasts treated with IGF-I was significantly increased (P < 0.05) compared with that in medium from untreated cultures; concomitantly, cell-associated IGFBP-3 was significantly decreased (P < 0.05). [Ser24]IGF-I (reduced affinity for IGF receptors) also increased secreted IGFBP-3 and decreased cell- associated IGFBP-3. In contrast, IGFBP-3 concentrations in medium conditioned by fibroblasts treated with B-chain IGF-I (reduced affinity for IGFBPs) were not significantly increased, and cell-associated IGFBP- 3 was unchanged. Heparin, which releases proteins attached to cell surface proteoglycans, increased medium concentrations of IGFBP-3 and decreased IGFBP-3 binding to fibroblasts. An IGFBP of 29-31 kilodaltons (kDa) showed a pattern of regulation similar to that of IGFBP-3, while a third IGFBP, of 24 kDa, was decreased in IGF-I- and [Ser24]IGF-I- conditioned medium and unchanged by B-chain IGF-I and heparin. Preincubation with transforming growth factor-beta 1 (TGF beta 1), which stimulates fibroblast IGFBP-3 production, or human serum-derived IGFBP-3 did not increase cell-associated IGFBP-3. Analysis of total RNA isolated from fibroblasts revealed that IGFBP-3 mRNA was increased by TGF beta 1, but not by IGF-I. These data suggest that IGFs and TGF beta 1 release fibroblast IGFBPs by distinct mechanisms: IGFs by binding and subsequent release of cell-associated IGFBP-3 and 29- to 31-kDa IGFBP, and TGF beta 1 by increased de novo synthesis of IGFBP-3.

This article has been cited by other articles:

				S. Jogie-Brahim, D. Feldman, and Y. Oh Unraveling Insulin-Like Growth Factor Binding Protein-3 Actions in Human Disease Endocr. Rev., August 1, 2009; 30(5): 417 - 437. [Abstract] [Full Text] [PDF]

				J. L. Martin and S. Jambazov Insulin-Like Growth Factor Binding Protein-3 in Extracellular Matrix Stimulates Adhesion of Breast Epithelial Cells and Activation of p44/42 Mitogen-Activated Protein Kinase Endocrinology, September 1, 2006; 147(9): 4400 - 4409. [Abstract] [Full Text] [PDF]

				I. Peters, I. Tossidou, J. Achenbach, R. Woroniecki, M. Mengel, J.-K. Park, M. Paschy, K. de Groot, H. Haller, and M. Schiffer IGF-Binding Protein-3 Modulates TGF-beta/BMP-Signaling in Glomerular Podocytes J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1644 - 1656. [Abstract] [Full Text] [PDF]

				K. Izumi, D. Kurosaka, T. Iwata, Y. Oguchi, Y. Tanaka, Y. Mashima, and K. Tsubota Involvement of Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 in Corneal Fibroblasts during Corneal Wound Healing Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 591 - 598. [Abstract] [Full Text] [PDF]

				X. F. Lu, X. G. Jiang, Y. B. Lu, J. H. Bai, and Z. B. Mao Characterization of a Novel Positive Transcription Regulatory Element That Differentially Regulates the Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Gene in Senescent Cells J. Biol. Chem., June 17, 2005; 280(24): 22606 - 22615. [Abstract] [Full Text] [PDF]

				J. Beattie, K. Phillips, J. H Shand, M. Szymanowska, D. J Flint, and G. J Allan Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein -3/5 (IGFBP-3/5) heparin axis J. Mol. Endocrinol., February 1, 2005; 34(1): 163 - 175. [Abstract] [Full Text] [PDF]

				K.-W. Lee, B. Liu, L. Ma, H. Li, P. Bang, H. P. Koeffler, and P. Cohen Cellular Internalization of Insulin-like Growth Factor Binding Protein-3: DISTINCT ENDOCYTIC PATHWAYS FACILITATE RE-UPTAKE AND NUCLEAR LOCALIZATION J. Biol. Chem., January 2, 2004; 279(1): 469 - 476. [Abstract] [Full Text] [PDF]

				J. L. Martin, S. M. Weenink, and R. C. Baxter Insulin-like Growth Factor-binding Protein-3 Potentiates Epidermal Growth Factor Action in MCF-10A Mammary Epithelial Cells. INVOLVEMENT OF p44/42 AND p38 MITOGEN-ACTIVATED PROTEIN KINASES J. Biol. Chem., January 24, 2003; 278(5): 2969 - 2976. [Abstract] [Full Text] [PDF]

				S. M. Firth and R. C. Baxter Cellular Actions of the Insulin-Like Growth Factor Binding Proteins Endocr. Rev., December 1, 2002; 23(6): 824 - 854. [Abstract] [Full Text] [PDF]

				J. G. Simmons, J. B. Pucilowska, T. O. Keku, and P. K. Lund IGF-I and TGF-beta 1 have distinct effects on phenotype and proliferation of intestinal fibroblasts Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G809 - G818. [Abstract] [Full Text] [PDF]

				A. J. Butt, K. A. Fraley, S. M. Firth, and R. C. Baxter IGF-Binding Protein-3-Induced Growth Inhibition and Apoptosis Do Not Require Cell Surface Binding and Nuclear Translocation in Human Breast Cancer Cells Endocrinology, July 1, 2002; 143(7): 2693 - 2699. [Abstract] [Full Text] [PDF]

				S. M. Firth, F. MCDougall, A. J. MCLachlan, and R. C. Baxter Impaired Blockade of Insulin-Like Growth Factor I (IGF-I)-Induced Hypoglycemia by IGF Binding Protein-3 Analog with Reduced Ternary Complex-Forming Ability Endocrinology, May 1, 2002; 143(5): 1669 - 1676. [Abstract] [Full Text] [PDF]

				R. Rajah, K.-W. Lee, and P. Cohen Insulin-like Growth Factor Binding Protein-3 Mediates Tumor Necrosis Factor-{alpha}-induced Apoptosis: Role of Bcl-2 Phosphorylation Cell Growth Differ., April 1, 2002; 13(4): 163 - 171. [Abstract] [Full Text] [PDF]

				D. R. Clemmons Use of Mutagenesis to Probe IGF-Binding Protein Structure/Function Relationships Endocr. Rev., December 1, 2001; 22(6): 800 - 817. [Abstract] [Full Text] [PDF]

				S. M. Twigg, M. M. Chen, A. H. Joly, S. D. Chakrapani, J. Tsubaki, H.-S. Kim, Y. Oh, and R. G. Rosenfeld Advanced Glycosylation End Products Up-Regulate Connective Tissue Growth Factor (Insulin-Like Growth Factor-Binding Protein-Related Protein 2) in Human Fibroblasts: A Potential Mechanism for Expansion of Extracellular Matrix in Diabetes Mellitus Endocrinology, May 1, 2001; 142(5): 1760 - 1769. [Abstract] [Full Text]

				J. L. Martin and S. L. Pattison Insulin-Like Growth Factor Binding Protein-3 Is Regulated by Dihydrotestosterone and Stimulates Deoxyribonucleic Acid Synthesis and Cell Proliferation in LNCaP Prostate Carcinoma Cells Endocrinology, July 1, 2000; 141(7): 2401 - 2409. [Abstract] [Full Text] [PDF]

				P. Cohen, R. Rajah, J. Rosenbloom, and D. J. Herrick IGFBP-3 mediates TGF-beta 1-induced cell growth in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L545 - L551. [Abstract] [Full Text] [PDF]

				J. A. Coverley, J. L. Martin, and R. C. Baxter The Effect of Phosphorylation by Casein Kinase 2 on the Activity of Insulin-Like Growth Factor-Binding Protein-3 Endocrinology, February 1, 2000; 141(2): 564 - 570. [Abstract] [Full Text] [PDF]

				M. Bruyninx, B. Hennuy, A. Cornet, P. Houssa, M. Daukandt, E. Reiter, J. Poncin, J. Closset, and G. Hennen A Novel Gene Overexpressed in the Prostate of Castrated Rats: Hormonal Regulation, Relationship to Apoptosis and to Acquired Prostatic Cell Androgen Independence Endocrinology, October 1, 1999; 140(10): 4789 - 4799. [Abstract] [Full Text]

				J. L. Martin and R. C. Baxter Oncogenic ras Causes Resistance to the Growth Inhibitor Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) in Breast Cancer Cells J. Biol. Chem., June 4, 1999; 274(23): 16407 - 16411. [Abstract] [Full Text] [PDF]

				Y. Yamanaka, J. L. Fowlkes, E. M. Wilson, R. G. Rosenfeld, and Y. Oh Characterization of Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) Binding to Human Breast Cancer Cells: Kinetics of IGFBP-3 Binding and Identification of Receptor Binding Domain on the IGFBP-3 Molecule Endocrinology, March 1, 1999; 140(3): 1319 - 1328. [Abstract] [Full Text]

				H. Olivecrona, A. Hilding, C. Ekström, H. Barle, B. Nyberg, C. Möller, P. J. Delhanty, R. C. Baxter, B. Angelin, T. J. Ekström, et al. Acute and Short-Term Effects of Growth Hormone on Insulin-Like Growth Factors and Their Binding Proteins: Serum Levels and Hepatic Messenger Ribonucleic Acid Responses in Humans J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 553 - 560. [Abstract] [Full Text]

				W. A. Price Peptide Growth Factors Regulate Insulin-Like Growth Factor Binding Protein Production by Fetal Rat Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., February 1, 1999; 20(2): 332 - 341. [Abstract] [Full Text]

				L. J. Schedlich, T. F. Young, S. M. Firth, and R. C. Baxter Insulin-like Growth Factor-binding Protein (IGFBP)-3 and IGFBP-5 Share a Common Nuclear Transport Pathway in T47D Human Breast Carcinoma Cells J. Biol. Chem., July 17, 1998; 273(29): 18347 - 18352. [Abstract] [Full Text] [PDF]

				S. S. Huang and J. S. Huang A Pentacosapeptide (CKS-25) Homologous to Retroviral Envelope Proteins Possesses a Transforming Growth Factor-beta Activity J. Biol. Chem., February 27, 1998; 273(9): 4815 - 4818. [Abstract] [Full Text] [PDF]

				S. M. Firth, U. Ganeshprasad, and R. C. Baxter Structural Determinants of Ligand and Cell Surface Binding of Insulin-like Growth Factor-binding Protein-3 J. Biol. Chem., January 30, 1998; 273(5): 2631 - 2638. [Abstract] [Full Text] [PDF]

				V. C. Russo, L. A. Bach, A. J. Fosang, N. L. Baker, and G. A. Werther Insulin-Like Growth Factor Binding Protein-2 Binds to Cell Surface Proteoglycans in the Rat Brain Olfactory Bulb Endocrinology, November 1, 1997; 138(11): 4858 - 4867. [Abstract] [Full Text] [PDF]

				S. M. Leal, Q. Liu, S. S. Huang, and J. S. Huang The Type V Transforming Growth Factor beta  Receptor Is the Putative Insulin-like Growth Factor-binding Protein 3 Receptor J. Biol. Chem., August 15, 1997; 272(33): 20572 - 20576. [Abstract] [Full Text] [PDF]

				M. M. Rechler Editorial: Growth Inhibition by Insulin-Like Growth Factor (IGF) Binding Protein-3--What's IGF Got To Do with It? Endocrinology, July 1, 1997; 138(7): 2645 - 2647. [Full Text] [PDF]

				R. Rajah, B. Valentinis, and P. Cohen Insulin-like Growth Factor (IGF)-binding Protein-3 Induces Apoptosis and Mediates the Effects of Transforming Growth Factor-beta 1 on Programmed Cell Death through a p53- and IGF-independent Mechanism J. Biol. Chem., May 2, 1997; 272(18): 12181 - 12188. [Abstract] [Full Text] [PDF]

				H. Salahifar, R. C. Baxter, and J. L. Martin Insulin-like Growth Factor Binding Protein (IGFBP)-3 Protease Activity Secreted by MCF-7 Breast Cancer Cells: Inhibition by IGFs Does Not Require IGF-IGFBP Interaction Endocrinology, April 1, 1997; 138(4): 1683 - 1690. [Abstract] [Full Text] [PDF]

				B. C. Villafuerte, W. Zhao, A. C. Herington, R. Saffery, and L. S. Phillips Identification of an Insulin-responsive Element in the Rat Insulin-like Growth Factor-binding Protein-3 Gene J. Biol. Chem., February 21, 1997; 272(8): 5024 - 5030. [Abstract] [Full Text] [PDF]

				J. L. Fowlkes and D. M. Serra Characterization of Glycosaminoglycan-binding Domains Present in Insulin-like Growth Factor-binding Protein-3 J. Biol. Chem., June 21, 1996; 271(25): 14676 - 14679. [Abstract] [Full Text] [PDF]

				T. Arai, J. Clarke, A. Parker, W. Busby Jr., T. Nam, and D. R. Clemmons Substitution of Specific Amino Acids in Insulin-like Growth Factor (IGF) Binding Protein 5 Alters Heparin Binding and Its Change in Affinity for IGF-I in Response to Heparin J. Biol. Chem., March 15, 1996; 271(11): 6099 - 6106. [Abstract] [Full Text] [PDF]

				H. Huynh, X. Yang, and M. Pollak Estradiol and Antiestrogens Regulate a Growth Inhibitory Insulin-like Growth Factor Binding Protein 3 Autocrine Loop in Human Breast Cancer Cells J. Biol. Chem., January 12, 1996; 271(2): 1016 - 1021. [Abstract] [Full Text] [PDF]

				Y. Oh, H. L. Müller, L. Ng, and R. G. Rosenfeld Transforming Growth Factor- [IMAGE]-induced Cell Growth Inhibition in Human Breast Cancer Cells Is Mediated through Insulin-like Growth Factor-binding Protein-3 Action J. Biol. Chem., June 9, 1995; 270(23): 13589 - 13592. [Abstract] [Full Text] [PDF]

				L. J. Schedlich, S. L. Le Page, S. M. Firth, L. J. Briggs, D. A. Jans, and R. C. Baxter Nuclear Import of Insulin-like Growth Factor-binding Protein-3 and -5 Is Mediated by the Importin beta Subunit J. Biol. Chem., July 28, 2000; 275(31): 23462 - 23470. [Abstract] [Full Text] [PDF]

				A. J. Butt, S. M. Firth, M. A. King, and R. C. Baxter Insulin-like Growth Factor-binding Protein-3 Modulates Expression of Bax and Bcl-2 and Potentiates p53-independent Radiation-induced Apoptosis in Human Breast Cancer Cells J. Biol. Chem., December 8, 2000; 275(50): 39174 - 39181. [Abstract] [Full Text] [PDF]