Yeldag Gulcen, Rice Alistair, Del Río Hernández Armando
Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Cancers (Basel). 2018 Nov 28;10(12):471. doi: 10.3390/cancers10120471.
The progression of cancer is associated with alterations in the tumor microenvironment, including changes in extracellular matrix (ECM) composition, matrix rigidity, hypervascularization, hypoxia, and paracrine factors. One key malignant phenotype of cancer cells is their ability to resist chemotherapeutics, and elements of the ECM can promote chemoresistance in cancer cells through a variety of signaling pathways, inducing changes in gene expression and protein activity that allow resistance. Furthermore, the ECM is maintained as an environment that facilitates chemoresistance, since its constitution modulates the phenotype of cancer-associated cells, which themselves affect the microenvironment. In this review, we discuss how the properties of the tumor microenvironment promote chemoresistance in cancer cells, and the interplay between these external stimuli. We focus on both the response of cancer cells to the external environment, as well as the maintenance of the external environment, and how a chemoresistant phenotype emerges from the complex signaling network present.
癌症的进展与肿瘤微环境的改变相关，包括细胞外基质（ECM）组成、基质硬度、血管过度增生、缺氧以及旁分泌因子的变化。癌细胞的一个关键恶性表型是其对化疗药物的抵抗能力，而ECM的成分可通过多种信号通路促进癌细胞的化疗耐药性，诱导基因表达和蛋白质活性的变化从而产生耐药性。此外，ECM维持着有利于化疗耐药性的环境，因为其组成调节癌症相关细胞的表型，而这些细胞本身又会影响微环境。在本综述中，我们讨论肿瘤微环境的特性如何促进癌细胞的化疗耐药性，以及这些外部刺激之间的相互作用。我们关注癌细胞对外部环境的反应，以及外部环境的维持，以及耐药表型如何从存在的复杂信号网络中出现。
