Home
Resources
Publications
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

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

Janet L Martin, Stan Jambazov

Endocrinology. 2006 Sep;147(9):4400-9.

PMID: 16763062

Abstract:

IGF-binding protein-3 (IGFBP-3) is a multifunctional protein that regulates the potent mitogenic and antiapoptotic effects of IGF-I and IGF-II and exerts bioactivity independent of modulating IGF receptor activation. Previous studies have shown that in solution, IGFBP-3 binds constituent proteins of the extracellular matrix (ECM) such as fibronectin and collagen and is present in ECM deposited by fibroblasts in vitro; however, binding of IGFBP-3 to matrix has not been characterized, nor has its function in this environment been investigated. In this study, we show that IGFBP-3 binds to ECM deposited by human breast epithelial and cancer cells and neonatal human fibroblasts. IGF-I and heparin blocked binding of IGFBP-3 to matrix when added with the binding protein but were unable to displace IGFBP-3 already bound to the matrix. IGF-I bound to matrix-immobilized IGFBP-3 with approximately 25-fold reduced affinity compared with IGFBP-3 in solution. Mutation of the C-terminal basic domain of IGFBP-3 (228KGRKR-->MDGEA) resulted in markedly reduced binding to matrix compared with wild-type IGFBP-3, whereas mutation of the adjacent consensus heparin-binding domain (220KKK-->HSR) had relatively little effect. In the presence of matrix-bound IGFBP-3, adhesion of breast epithelial cells was increased by approximately 25%, and activation of the signaling pathway intermediate p44/42 MAPK was enhanced greater than 3-fold. These results indicate a previously unrecognized and potentially important role for IGFBP-3 in the extracellular matrix.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248434	Fibronectin solution human fibroblasts			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: