Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10903972 | Experimental Cell Research | 2015 | 12 Pages |
Abstract
Cancer stem cell (CSC) or tumor initiating cell (TIC) plays an important role in tumor progression and metastasis. Biophysical forces in tumor microenvironment have an important effect on tumor formation and development. In this study, the potential effect of matrix stiffness on the biological characteristics of human head and neck squamous cell carcinoma (HNSCC) TICs, especially the enrichment of HNSCC TICs, was investigated under three-dimensional (3D) culture conditions by means of alginate gel (ALG) beads with different matrix stiffnesses. ALG beads with soft (21Â kPa), moderate (70Â kPa) and hard (105Â kPa) stiffness were generated by changing alginate concentration. It was found that significant HNSCC TIC enrichment was achieved in the ALG beads with moderate matrix stiffness (70Â kPa). The gene expression of stemness markers Oct3/4 and Nanog, TIC markers CD44 and ABCG2 was enhanced in cells under this moderate (70Â kPa) stiffness. HNSCC TIC proportion was also highly enriched under moderate matrix stiffness, accompanying with higher tumorigenicity, metastatic ability and drug resistance. And it was also found that the possible molecular mechanism underlying the regulated TIC properties by matrix stiffness under 3D culture conditions was significantly different from 2D culture condition. Therefore, the results achieved in this study indicated that 3D biophysical microenvironment had an important effect on TIC characteristics and alginate-based biomimetic scaffolds could be utilized as a proper platform to investigate the interaction between tumor cells and 3D microenvironment.
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Authors
Chang Liu, Yang Liu, Xiao-xi Xu, Hao Wu, Hong-guo Xie, Li Chen, Ting Lu, Li Yang, Xin Guo, Guang-wei Sun, Wei Wang, Xiao-jun Ma, Xin He,