State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
J Cell Physiol. 2018 Apr;233(4):3407-3417. doi: 10.1002/jcp.26189. Epub 2017 Oct 27.
Tumor tissue tends to stiffen during solid tumor progression. Substrate stiffness is known to alter cell behaviors, such as proliferation and migration, during which angiogenesis is requisite. Mono- and co-culture systems of lung cancer cell line A549 and human umbilical vein endothelial cells (HUVECs), on polydimethylsiloxane substrates (PDMS) with varying stiffness, were used for investigating the effects of substrate stiffness on the migration and angiogenesis of lung cancer. The expressions of matrix metalloproteinases (MMPs) and angiogenesis-related growth factors were up-regulated with the increase of substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase (TIMPs) were down-regulated with increasing substrate stiffness. Our data not only suggested that stiff substrate may promote the migration and angiogenesis capacities of lung cancer, but also suggested that therapeutically targeting lung tumor stiffness or response of ECs to lung tumor stiffness may help reduce migration and angiogenesis of lung tumor.
肿瘤组织在实体瘤进展过程中往往会变硬。已知基质硬度会改变细胞的行为，如增殖和迁移，而血管生成是必需的。在具有不同硬度的聚二甲基硅氧烷（PDMS）底物上，使用肺癌细胞系 A549 和人脐静脉内皮细胞（HUVEC）的单培养和共培养系统，研究了基质硬度对肺癌细胞迁移和血管生成的影响。随着基质硬度的增加，基质金属蛋白酶（MMPs）和血管生成相关生长因子的表达上调，而基质金属蛋白酶抑制剂（TIMP）的表达下调。我们的数据不仅表明硬基质可能促进肺癌的迁移和血管生成能力，还表明靶向肺癌硬度或内皮细胞对肺癌硬度的反应的治疗方法可能有助于减少肺癌的迁移和血管生成。
