Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA; University of Illinois Cancer Center, Chicago, IL, USA.
Semin Cell Dev Biol. 2019 May;89:157-166. doi: 10.1016/j.semcdb.2018.06.005. Epub 2018 Jul 13.
Tumor progression and dissemination critically depend on support from the tumor microenvironment, the ensemble of cellular and acellular components surrounding and interacting with tumor cells. The extracellular matrix (ECM), the complex scaffolding of hundreds of proteins organizing cells in tissues, is a major component of the tumor microenvironment. It orchestrates cellular processes including proliferation, migration, and invasion, that are highly dysregulated during cancer progression. Alterations in ECM abundance, integrity, and mechanical properties have been correlated with poorer prognosis for cancer patients. Yet the ECM proteome, or "matrisome," of tumors remained until recently largely unexplored. This review will present the recent developments in computational and proteomic technologies that have allowed the comprehensive characterization of the ECM of different tumor types and microenvironmental niches. These approaches have resulted in the definition of protein signatures distinguishing tumors from normal tissues, tumors of different stages, primary from secondary tumors, and tumors from other diseased states such as fibrosis. Moreover, recent studies have demonstrated that the levels of expression of certain genes encoding ECM and ECM-associated proteins is prognostic of cancer patient survival and can thus serve as biomarkers. Last, proteomic studies have permitted the identification of novel ECM proteins playing functional roles in cancer progression. Such proteins have the potential to be exploited as therapeutic targets.
肿瘤的进展和扩散严重依赖于肿瘤微环境的支持,肿瘤微环境是由围绕和与肿瘤细胞相互作用的细胞和细胞外成分组成的整体。细胞外基质 (ECM) 是组织中数百种蛋白的复杂支架,是肿瘤微环境的主要组成部分。它协调细胞过程,包括增殖、迁移和侵袭,这些过程在癌症进展过程中高度失调。ECM 丰度、完整性和力学性质的改变与癌症患者预后不良相关。然而,直到最近,肿瘤的 ECM 蛋白质组(即“基质组”)仍然在很大程度上未被探索。这篇综述将介绍最近在计算和蛋白质组学技术方面的发展,这些技术使得对不同肿瘤类型和微环境龛位的 ECM 进行全面表征成为可能。这些方法导致了区分肿瘤与正常组织、不同阶段肿瘤、原发性肿瘤与继发性肿瘤以及肿瘤与其他疾病状态(如纤维化)的蛋白质特征的定义。此外,最近的研究表明,某些编码 ECM 和 ECM 相关蛋白的基因的表达水平是癌症患者生存的预后指标,因此可以作为生物标志物。最后,蛋白质组学研究鉴定了在癌症进展中发挥功能作用的新型 ECM 蛋白。这些蛋白有可能被开发为治疗靶点。