Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer
Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer
复制标题
减少肝转移僵硬度可改善转移性结直肠癌对贝伐珠单抗的反应
DOI：
10.1016/j.ccell.2020.05.005
复制
发表时间：
2020-06-08
期刊：
影响因子：
50.3
通讯作者：
Schmidt, Thomas
中科院分区：
文献类型：
--
作者：
Shen, Ying;Wang, Xiaohong;Schmidt, Thomas
肿瘤受其微环境的力学特性影响。使用患者样本和原子力显微镜，我们发现肝转移瘤的组织硬度高于原发性结直肠肿瘤。高度活化的转移相关成纤维细胞增加组织硬度，从而增强血管生成和抗血管生成治疗抵抗。靶向肾素-血管紧张素系统的药物，通常用于治疗高血压，抑制成纤维细胞收缩和细胞外基质沉积，从而减少肝转移硬化，增加贝伐单抗的抗血管生成作用。接受贝伐单抗治疗的患者在同时接受肾素-血管紧张素抑制剂治疗时显示出延长的生存期，突出了调节治疗方案的机械微环境的重要性。
Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Drugs targeting the renin-angiotensin system, normally prescribed to treat hypertension, inhibit fibroblast contraction and extracellular matrix deposition, thereby reducing liver metastases stiffening and increasing the anti-angiogenic effects of bevacizumab. Patients treated with bevacizumab showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, highlighting the importance of modulating the mechanical microenvironment for therapeutic regimens.