Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells.
Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells.
复制标题
开发仿生硫酸软骨素修饰水凝胶以增强肿瘤细胞的转移
DOI：
10.1038/srep29858
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发表时间：
2016-07-19
影响因子：
4.6
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Liu Y;Wang S;Sun D;Liu Y;Liu Y;Wang Y;Liu C;Wu H;Lv Y;Ren Y;Guo X;Sun G;Ma X
肿瘤转移对抗癌治疗的耐药性是癌症患者死亡的主要原因。因此，有必要建立一种能够准确再现肿瘤组织病理生理特征的肿瘤转移模型。在这项研究中，硫酸软骨素（CS）修饰的藻酸盐水凝胶珠（ALG-CS）开发模拟体内肿瘤微环境与CS的表达异常增加，促进肿瘤细胞转移。CS对海藻酸钠水凝胶的改性机理是通过钙离子的配位作用使CS与海藻酸钠分子发生交联，从而使ALG-CS具有与传统海藻酸钠微球（ALG）明显不同的物理特性。量子化学计算表明，除了传统的蛋盒结构外，ALG-CS还形成了基于两种聚合物相互作用的新型不对称蛋盒结构。此外，ALG-CS中的肿瘤细胞转移显著增强，这通过MMP基因和蛋白的表达增加以及肿瘤细胞体外侵袭能力的增强来证实。因此，ALG-CS可以成为一种方便有效的3D仿生支架，可用于构建标准化的肿瘤转移模型，用于肿瘤研究和抗癌药物筛选。
Tumor metastasis with resistance to anticancer therapies is the main cause of death in cancer patients. It is necessary to develop reliable tumor metastasis models that can closely recapitulate the pathophysiological features of the native tumor tissue. In this study, chondroitin sulfate (CS)-modified alginate hydrogel beads (ALG-CS) are developed to mimic thein vivotumor microenvironment with an abnormally increased expression of CS for the promotion of tumor cell metastasis. The modification mechanism of CS on alginate hydrogel is due to the cross-linking between CS and alginate molecules via coordination of calcium ions, which enables ALG-CS to possess significantly different physical characteristics than the traditional alginate beads (ALG). And quantum chemistry calculations show that in addition to the traditional egg-box structure, novel asymmetric egg-box-like structures based on the interaction between these two kinds of polymers are also formed within ALG-CS. Moreover, tumor cell metastasis is significantly enhanced in ALG-CS compared with that in ALG, as confirmed by the increased expression of MMP genes and proteins and greaterin vitroinvasion ability. Therefore, ALG-CS could be a convenient and effective 3D biomimetic scaffold that would be used to construct standardized tumor metastasis models for tumor research and anticancer drug screening.