Sounni Nor Eddine, Paye Alexandra, Host Lorin, Noël Agnès
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer, University of Liege Liège, Belgium.
Front Pharmacol. 2011 May 13;2:111. doi: 10.3389/fphar.2011.00111. eCollection 2011.
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.
血管系统的发育依赖于多种不同分子家族的协同活动，这些分子家族包括生长因子及其受体、细胞黏附分子、细胞外基质（ECM）分子和蛋白水解酶。基质金属蛋白酶（MMPs）是一类ECM降解酶，在生理性和病理性血管生成中均不可或缺。越来越多的证据表明，膜型MMPs（MT-MMPs）在血管系统的稳定、成熟和渗漏中起直接作用。我们对MT-MMP与细胞外及细胞表面分子相互作用的性质及其在血管壁和血管周围基质中的多种作用的理解，可能为病理性条件下血管细胞-ECM相互作用及细胞命运决定的潜在机制提供新的见解。MT-MMP与ECM相互作用对血管渗漏的调节也可能为肿瘤药物递送带来新的靶向机会。本综述将阐明MT1-MMP和MT4-MMP在与癌症进展相关的血管系统改变中的新作用。
