|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00097
Research Article |
Division of Surgery, Department of Hospital Medicine, Bristol Royal Infirmary, Bristol, BS2 8HW, UK
* Author for correspondence (e-mail: claire.m.perks{at}bristol.ac.uk)
Accepted 6 August 2002
The insulin-like growth factor binding proteins (IGFBPs) have IGF-independent differential effects on cell function. We investigated whether they can affect integrin-receptor-mediated cell attachment to different extracellular matrix (ECM) components in Hs578T cells.
Cell attachment to a general ECM gel was unaffected by IGFBP-1 and -6 but was significantly increased by IGFBP-4 and -5 and decreased by IGFBP-2 and -3. Similar results were obtained for attachment to laminin or collagen type IV. Attachment to fibronectin, however, was increased by IGFBP-3 and decreased by IGFBP-5. The actions of IGFBP-3 and -5 on cell attachment to ECM were lost in the presence of a soluble Arg-Gly-Asp (RGD)-containing fibronectin fragment. Thrombospondin reversed the actions of IGFBP-3 on cell attachment, but IGFBP-5 still increased cell attachment.
On plastic, neither IGFBP-3 nor -5 alone affected cell viability; although ceramide-induced apoptosis was enhanced by IGFBP-3 but reduced by IGFBP-5. The presence of RGD reversed the action of IGFBP-5 on cell death but attenuated that of IGFBP-3. With cells grown on fibronectin, the action of IGFBP-3 was reversed, and it conferred cell survival, whereas the survival effect of IGFBP-5 was lost.
In summary we have demonstrated that IGFBP-3 and -5 both have intrinsic effects on cell survival. In each case the presence of fibronectin or fibronectin fragments determines whether susceptibility to apoptosis is increased or decreased. These effects on cell survival are paralleled by acute effects on integrin receptor function; IGFBP-3 and -5 were able to either enhance or inhibit cell attachment in the presence of fibronectin. Cell survival is tightly controlled by cues from the ECM and from growth factors, particularly the IGFs. Our findings indicate that, in addition to being crucial modulators of IGF actions, the IGFBPs have direct actions on cell attachment and survival that are specific and dependent upon the matrix components present.
Key words: IGFBP, Cell adhesion, ECM, Breast epithelia, Apoptosis, Integrin, Fibronectin
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
C. Burrows, J. M. P. Holly, N. J. Laurence, E. G. Vernon, J. V. Carter, M. A. Clark, J. McIntosh, C. McCaig, Z. E. Winters, and C. M. Perks Insulin-Like Growth Factor Binding Protein 3 Has Opposing Actions on Malignant and Nonmalignant Breast Epithelial Cells that Are Each Reversible and Dependent upon Cholesterol-Stabilized Integrin Receptor Complexes Endocrinology, July 1, 2006; 147(7): 3484 - 3500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G Renehan, M. Harvie, and A. Howell Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr. Relat. Cancer, June 1, 2006; 13(2): 273 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, P. Yin, L. A. Bach, and C. Duan Several Acidic Amino Acids in the N-domain of Insulin-like Growth Factor-binding Protein-5 Are Important for Its Transactivation Activity J. Biol. Chem., May 19, 2006; 281(20): 14184 - 14191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P J Jenkins, S Khalaf, W Ogunkolade, K McCarthy, T David, R E Hands, D Davies, and S A Bustin Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis Endocr. Relat. Cancer, December 1, 2005; 12(4): 891 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Fleming, B J Leibowitz, D E Kerr, and W S Cohick IGF-I differentially regulates IGF-binding protein expression in primary mammary fibroblasts and epithelial cells J. Endocrinol., July 1, 2005; 186(1): 165 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Butt, K. A. Dickson, S. Jambazov, and R. C. Baxter Enhancement of Tumor Necrosis Factor-{alpha}-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells Endocrinology, July 1, 2005; 146(7): 3113 - 3122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Jacobsen, S. A. Schittone, J. K. Richer, and K. B. Horwitz Progesterone-Independent Effects of Human Progesterone Receptors (PRs) in Estrogen Receptor-Positive Breast Cancer: PR Isoform-Specific Gene Regulation and Tumor Biology Mol. Endocrinol., March 1, 2005; 19(3): 574 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hu, R. Xu, G. Zhang, J. Jin, Z. M. Szulc, J. Bielawski, Y. A. Hannun, L. M. Obeid, and C. Mao Golgi Fragmentation Is Associated with Ceramide-induced Cellular Effects Mol. Biol. Cell, March 1, 2005; 16(3): 1555 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Cobb, D. A. M. Salih, I. Gonzalez, G. Tripathi, E. J. Carter, F. Lovett, C. Holding, and J. M. Pell Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function J. Cell Sci., May 1, 2004; 117(9): 1737 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu, S. Li, Y. Zhao, T. J. Maures, P. Yin, and C. Duan Evidence That IGF Binding Protein-5 Functions as a Ligand-Independent Transcriptional Regulator in Vascular Smooth Muscle Cells Circ. Res., March 19, 2004; 94(5): e46 - e54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, B. Yan, S. Li, and C. Duan Fibronectin Binds Insulin-like Growth Factor-binding Protein 5 and Abolishes Its Ligand-dependent Action on Cell Migration J. Biol. Chem., February 6, 2004; 279(6): 4269 - 4277. [Abstract] [Full Text] [PDF]
|
|
