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.

肿瘤受其微环境的机械性能影响。使用患者样本和原子力显微镜检查，我们发现肝脏转移灶中的组织硬度高于原发性结肠直肠肿瘤。高度激活的与转移相关的成纤维细胞可增加组织硬度，从而增强血管生成和抗血管生成治疗的抵抗力。通常针对肾素-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，从而减少肝转移瘤变硬并增强贝伐单抗的抗血管生成作用。用贝伐单抗治疗的患者在同时使用肾素-血管紧张素抑制剂治疗时表现出延长的生存期，这突出了调节机械微环境对治疗方案的重要性。