MT-MMPs as regulators of vessel stability associated with angiogenesis

Abstract

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The development of vascular system depends on the coordinated activity of a number of distinct families of molecules including growth factors and their receptors, cell adhesion molecules, extracellular matrix (ECM) molecules and proteolytic enzymes. Matrix metalloproteases (MMPs) are a family of ECM degrading enzymes required for both physiological and pathological angiogenesis. Increasing evidence, point to a direct role of membrane type-MMPs (MT-MMPs) in vascular system stabilization, maturation and leakage. Our understanding of the nature of MT-MMP interaction with extracellular and cell surface molecules and their multiple roles in vessel walls and perivascular stroma may provide new insights into mechanisms underlying vascular cell-ECM interactions and cell fate decisions in pathological conditions. Regulation of vascular leakage by MT-MMP interactions with the ECM could also lead to novel targeting opportunities for drug delivery in tumor. This review will shed lights on the emerging roles of MT1-MMP and MT4-MMP in vascular system alterations associated with cancer progression.

Keywords

• Collagen
• interstitial fluid pressure
• MMPs
• MT-MMPs
• vessel permeability