Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Semin Cancer Biol. 2020 May;62:192-200. doi: 10.1016/j.semcancer.2019.09.004. Epub 2019 Sep 10.
Extracellular matrix (ECM) plays a central and dynamic role in the creation of tumor microenvironment. Herein we discuss the emerging biophysical and biochemical aspects of ECM buildup and proteolysis in cancer niche formation. Dysregulated ECM remodeling by cancer cells facilitate irreversible proteolysis and crosslinking, which in turn influence cell signaling, micro environmental cues, angiogenesis and tissue biomechanics. Further, we introduce the emerging roles of cancer microbiome in aberrant tumor ECM remodeling and membrane bound nano-sized vesicles called exosomes in creation of distant pre-metastatic niches. A detailed molecular and biophysical understanding of the ECM morphologies and its components such as key enzymes, structural and signaling molecules are critical in identifying the next generation of therapeutic and diagnostic targets in cancer.
细胞外基质 (ECM) 在肿瘤微环境的形成中起着核心和动态的作用。本文讨论了 ECM 生成和蛋白水解在癌症生态位形成中的新兴生物物理和生化方面。癌细胞中失调的 ECM 重塑促进了不可逆的蛋白水解和交联，进而影响细胞信号转导、微环境线索、血管生成和组织生物力学。此外，我们还介绍了癌症微生物组在异常肿瘤 ECM 重塑以及称为外泌体的膜结合纳米大小囊泡中在形成远处前转移生态位中的新兴作用。详细了解 ECM 形态及其成分（如关键酶、结构和信号分子）的分子和生物物理特性对于确定癌症的下一代治疗和诊断靶点至关重要。
