Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer.
Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer.
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DOI：
10.1242/dmm.004077
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发表时间：
2011-03
影响因子：
4.3
通讯作者：
Erler JT
中科院分区：
文献类型：
--
作者：
Cox TR;Erler JT
细胞外基质（ECM）的动态重塑对于发育、伤口愈合和正常器官的稳态是必不可少的。当ECM重塑变得过度或不受控制时，会出现危及生命的病理状况。在这个角度，我们专注于ECM重塑如何有助于纤维化疾病和癌症，这两个方面的临床治疗提出了挑战性的障碍，以说明细胞-ECM相互作用在这些条件的发病机制的重要性和复杂性。包括肺纤维化、系统性硬化症、肝硬化和心血管疾病在内的纤维化疾病占发达国家死亡人数的45%以上。ECM重塑对于肿瘤恶性和转移性进展也是至关重要的，其最终导致超过90%的癌症死亡。在这里，我们讨论了当前的方法和模型，用于理解和量化ECM提供的环境线索对疾病进展的影响，以及如何提高我们对这些病理条件下ECM重塑的理解对于发现新的治疗靶点和治疗策略至关重要。这只能通过使用适当的体外和体内模型来模拟疾病，并使用能够准确监测、成像和定量ECM的技术来实现。
Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.
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