Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
Carbohydr Polym. 2019 May 1;211:336-348. doi: 10.1016/j.carbpol.2019.01.115. Epub 2019 Feb 5.
In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer.
在肿瘤生物学中，人们普遍认为 3D 细胞培养而非 2D 细胞培养可以更好地模拟实体瘤的关键特征，包括细胞-细胞外基质（ECM）相互作用。在这项研究中，为了模拟乳腺癌的 ECM，通过腙键和光双重交联过程，从两种多价 HA 衍生物合成了透明质酸（HA）水凝胶。HA 水凝胶可在 120 秒内形成。水凝胶的形貌和力学性能与乳腺癌组织相似，并表现出谷胱甘肽和透明质酸酶双重响应的降解行为。生物学研究表明，HA 水凝胶能够支持乳腺癌 MCF-7 细胞的增殖和聚集。与 2D 培养相比，水凝胶培养的细胞中 VEGF、IL-8 和 bFGF 的表达水平显著升高。此外，与 2D 培养的细胞相比，水凝胶培养的细胞具有更强的迁移/侵袭能力和致瘤性。因此，HA 水凝胶是体外构建乳腺癌的一种有前途的 ECM 模拟基质。
