Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts
Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts
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DOI：
10.1002/adhm.201801587
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发表时间：
2019-05-01
影响因子：
10
通讯作者：
Zheng, Li
中科院分区：
文献类型：
--
作者：
Jiang, Tongmeng;Xu, Guojie;Zheng, Li
细胞外基质（ECM）的生化和物理特性控制细胞行为，但它们如何影响不需要附着的骨肉瘤细胞及其依赖贴壁的正常对应物（成骨细胞）尚未报道。在本研究中，与成骨细胞 hFOB1.19 细胞相比，使用四种具有不同粘附配体和硬度的支架（I 型胶原、基质胶、藻酸盐和琼脂糖）研究基质弹性和粘附对骨肉瘤 MG63 细胞的影响。 2D 胶片上的 MG63 细胞对 ECM 粘附敏感，类似于 2D 和 3D 培养的 hFOB1.19 的情况。然而，3D水凝胶中的骨肉瘤细胞对ECM弹性而不是粘附敏感，肿瘤增殖和恶性程度随基质刚性而变化。结果表明，骨肉瘤细胞可能在平坦的表面上采取不自然的特征。但在 3D 培养中，它们恢复了独立于粘附的正常状态，主要通过整合素介导的粘着斑途径受 ECM 弹性调节，这得到了体内研究的进一步证实。相比之下，成骨细胞和二维培养的骨肉瘤细胞主要受整合素介导的粘附连接途径调节的 ECM 生物活性的影响。这项研究可能为肿瘤/组织工程支架的合理设计提供新的见解。
Biochemical and physical properties of extracellular matrix (ECM) control cell behaviors, but how they affect osteosarcoma cells that do not require attachment and their normal counterparts (osteoblasts) that are anchorage-dependent has not been reported yet. In this study, the effects of matrix elasticity and adherence on osteosarcoma MG63 cells are investigated using four types of scaffolds (collagen type I, matrigel, alginate, and agarose) with varied adhesion ligands and rigidity, as compared with osteoblast hFOB1.19 cells. MG63 cells on 2D films are sensitive to ECM adherence, similar to the situation of hFOB1.19 cultured in both 2D and 3D. However, osteosarcoma cells in 3D hydrogels are sensitive to ECM elasticity rather than adherence, with tumor proliferation and malignancy varied with matrix rigidity. The results indicate that osteosarcomas cells might adopt unnatural characteristics on flat surfaces. But in 3D culture, they recover their normal state independent of adherence, as regulated mainly by ECM elasticity via the integrin-mediated focal adhesion pathway, which is further confirmed by in vivo studies. In contrast, osteoblasts and 2D cultured osteosarcoma cells are predominantly influenced by ECM bioactivity regulated by integrin-mediated adherens junction pathway. This study might provide new insights into rational design of scaffolds for tumor/tissue engineering.