Duffy M J, McGowan P M, Gallagher W M
Department of Pathology and Laboratory Medicine, St Vincent's University Hospital, Dublin 4, Ireland.
J Pathol. 2008 Feb;214(3):283-93. doi: 10.1002/path.2282.
The formation of distant metastasis is the main cause of morbidity and mortality in patients with cancer. The aim of this article is to review recent advances in molecular and clinical aspects of metastasis. Traditionally, genes encoding extracellular matrix (ECM) processing proteases, adhesion proteins, and motility factors were thought to be amongst the main mediators of metastasis. Recently, however, genes activated during the early stages of tumourigenesis were implicated in the process. Conversely, genes thought to be primarily involved in metastasis such as urokinase plasminogen (uPA) and certain matrix metalloproteases (MMPs) are now known to also play a role in the early steps of tumour progression, perhaps by stimulating cell proliferation and/or promoting angiogenesis. Paradoxically, certain endogenous protease inhibitors such as PAI-1 and TIMP-1 appear to promote cancer metastasis rather than inhibiting the process. These recent advances in our understanding should lead to the development of new molecular markers for predicting the likely formation of metastasis as well as the identification of new targets for anti-metastatic therapies.
远处转移的形成是癌症患者发病和死亡的主要原因。本文旨在综述转移在分子和临床方面的最新进展。传统上，编码细胞外基质（ECM）加工蛋白酶、黏附蛋白和运动因子的基因被认为是转移的主要介导因子。然而，最近发现肿瘤发生早期激活的基因也参与了这一过程。相反，现在已知一些原本被认为主要参与转移的基因，如尿激酶型纤溶酶原（uPA）和某些基质金属蛋白酶（MMPs），也在肿瘤进展的早期阶段发挥作用，可能是通过刺激细胞增殖和/或促进血管生成。矛盾的是，某些内源性蛋白酶抑制剂，如PAI-1和TIMP-1，似乎促进而不是抑制癌症转移。我们在认识上的这些最新进展应会促使开发新的分子标志物来预测转移的可能形成，并确定抗转移治疗的新靶点。
