Kelsh Rhiannon M, McKeown-Longo Paula J
Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York 12208, USA.
Trends Cancer Res. 2013 Jan 1;9:1-13.
The relationship between cancer progression and chronic inflammation is well documented but poorly understood. The innate immune system has long been recognized as the first line of defense against invading pathogens. More recently, endogenous molecules released from tissue matrix (Damage Associated Molecular Patterns [DAMPs]) following tissue injury or periods of active matrix remodeling have also been identified as regulators of innate immunity. DAMPs have been identified as ligands for Toll-like receptors (TLRs), a family of cell-surface proteins which regulate the immune response. TLRs have been identified on resident tissue cells as well as most tumor cells. Therefore, dysregulation of the innate immune response secondary to biochemical and mechanical driven changes in the extracellular matrix of the tumor microenvironment may be a critical component of the chronic inflammation associated with tumor progression. Here we review the role of extracellular matrix (ECM)-derived DAMPS in the activation of TLR4 signaling in the context of tumor progression. We also explore the various types of topographical changes that can lead to ECM-derived DAMPs and their contribution to TLR4 activation.
癌症进展与慢性炎症之间的关系已有充分记录，但人们对此了解甚少。长期以来，先天免疫系统一直被视为抵御入侵病原体的第一道防线。最近，组织损伤或活跃的基质重塑期后从组织基质释放的内源性分子（损伤相关分子模式[DAMPs]）也被确定为先天免疫的调节因子。DAMPs已被确定为Toll样受体（TLRs）的配体，Toll样受体是一类调节免疫反应的细胞表面蛋白。在驻留组织细胞以及大多数肿瘤细胞上都已发现TLRs。因此，肿瘤微环境细胞外基质中生化和机械驱动变化继发的先天免疫反应失调可能是与肿瘤进展相关的慢性炎症的关键组成部分。在此，我们综述了在肿瘤进展背景下细胞外基质（ECM）衍生的DAMPS在激活TLR4信号传导中的作用。我们还探讨了可导致ECM衍生DAMPs的各种地形变化类型及其对TLR4激活的贡献。
