Chin LiKang, Xia Yuntao, Discher Dennis E, Janmey Paul A
Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Physical Sciences in Oncology Center at Penn (PSOC@Penn), University of Pennsylvania, Philadelphia, PA 19104, USA; Clinical Research Center for Diabetes, Tokushima University Hospital, Tokushima 770-8503, Japan.
Physical Sciences in Oncology Center at Penn (PSOC@Penn), University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular & Cell Biophysics and NanoBioPolymers Labs, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Opin Chem Eng. 2016 Feb;11:77-84. doi: 10.1016/j.coche.2016.01.011. Epub 2016 Feb 16.
Tissue stiffness is tightly controlled under normal conditions, but changes with disease. In cancer, tumors often tend to be stiffer than the surrounding uninvolved tissue, yet the cells themselves soften. Within the past decade, and particularly in the last few years, there is increasing evidence that the stiffness of the extracellular matrix modulates cancer and stromal cell mechanics and function, influencing such disease hallmarks as angiogenesis, migration, and metastasis. This review briefly summarizes recent studies that investigate how cancer cells and fibrosis-relevant stromal cells respond to ECM stiffness, the possible sensing appendages and signaling mechanisms involved, and the emergence of novel substrates - including substrates with scar-like fractal heterogeneity - that mimic the mechanical environment of the cancer cell.
在正常情况下,组织硬度受到严格控制,但会随疾病发生变化。在癌症中,肿瘤往往比周围未受累组织更硬,但其细胞本身却会变软。在过去十年中,尤其是在最近几年,越来越多的证据表明,细胞外基质的硬度会调节癌细胞和基质细胞的力学特性及功能,影响血管生成、迁移和转移等疾病特征。本文综述简要总结了近期的研究,这些研究探讨了癌细胞和与纤维化相关的基质细胞如何响应细胞外基质硬度、涉及的可能传感附属物和信号传导机制,以及新型基质的出现——包括具有瘢痕样分形异质性的基质——这些基质模拟了癌细胞的力学环境。