The Role of the IGF-I Receptor in the Regulation of Matrix Metalloproteinases, Tumor Invasion and Metastasis

D. Zhang; A. A. Samani; P. Brodt

doi:10.1055/s-2004-814143

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2003; 35(11/12): 802-808
DOI: 10.1055/s-2004-814143

Review

The Role of the IGF-I Receptor in the Regulation of Matrix Metalloproteinases, Tumor Invasion and Metastasis

D. Zhang¹ , A. A. Samani¹ , P. Brodt¹

¹Department of Surgery (D.Z, A.S., P.B.) and Medicine (P.B.), McGill University Health Center, the Royal Victoria Hospital, Montreal, Quebec, Canada

Supported by grant # mop-10505 from the Canadian Institute for Health Research and by a Terry Fox New Frontiers initiative grant (to P.B.).

Abstract

The breakdown of the extracellular matrix (ECM) by proteinases is an essential step in the process of cancer invasion and metastasis. Malignant progression is frequently associated with upregulated production and/or activity of one or several ECM degrading proteinases. Prominent among them are the matrix metalloproteinases (MMPs). The MMPs constitute a family of structurally related, zinc-dependent endopeptidases collectively capable of degrading essentially all the components of the extracellular matrix. At present, 23 members of the human MMP gene family are known. The increased expression and/or activity of one or more members of this family have been documented in essentially all human malignancies and some have been implicated in the process of angiogenesis. Prominent among those are MMP-2 and MT1-MMP, two metalloproteinases that form a cell membrane-associated complex leading to MMP-2 activation and ECM proteolysis. Here, we review our data that identified the type 1 insulin-like growth factor receptor (IGF-IR) as a regulator of tumor invasion and the synthesis of MT1-MMP and MMP-2 and report on the signal transduction pathways that mediate this regulation. These findings are discussed in the context of a broader review of the role of the IGF-IR/IGF axis in the regulation of tumor invasion and metastasis.

Key words

IGF-I receptor - MT1-MMP - MMP-2 - Invasion - Metastasis

Full Text

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