https://scholars.lib.ntu.edu.tw/handle/123456789/384602
標題: | Acquisition of epithelial-mesenchymal transition and cancer stem-like phenotypes within chitosan-hyaluronan membrane-derived 3D tumor spheroids | 作者: | Huang, Y.-J. Hsu, S.-H. SHAN-HUI HSU |
關鍵字: | Cancer stem cell; Epithelial-mesenchymal transition; Hyaluronan; Multidrug resistance; Tumor spheroids | 公開日期: | 2014 | 卷: | 35 | 期: | 38 | 起(迄)頁: | 10070-10079 | 來源出版物: | Biomaterials | 摘要: | Cancer drug development has to go through rigorous testing and evaluation processes during pre-clinical invitro studies. However, the conventional two-dimensional (2D) invitro culture is often discounted by the insufficiency to present a more typical tumor microenvironment. The multicellular tumor spheroids have been a valuable model to provide more comprehensive assessment of tumor in response to therapeutic strategies. Here, we applied chitosan-hyaluronan (HA) membranes as a platform to promote three-dimensional (3D) tumor spheroid formation. The biological features of tumor spheroids of human non-small cell lung cancer (NSCLC) cells on chitosan-HA membranes were compared to those of 2D cultured cells invitro. The cells in tumor spheroids cultured on chitosan-HA membranes showed higher levels of stem-like properties and epithelial-mesenchymal transition (EMT) markers, such as NANOG, SOX2, CD44, CD133, N-cadherin, and vimentin, than 2D cultured cells. Moreover, they exhibited enhanced invasive activities and multidrug resistance by the upregulation of MMP2, MMP9, BCRC5, BCL2, MDR1, and ABCG2 as compared with 2D cultured cells. The grafting densities of HA affected the tumor sphere size and mRNA levels of genes on the substrates. These evidences suggest that chitosan-HA membranes may offer a simple and valuable biomaterial platform for rapid generation of tumor spheroids invitro as well as for further applications in cancer stem cell research and cancer drug screening. ? 2014 Elsevier Ltd. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84908102075&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/384602 |
DOI: | 10.1016/j.biomaterials.2014.09.010 | SDG/關鍵字: | Chitosan; Cytology; Diagnosis; Diseases; Drug products; Membranes; Stem cells; Tumors; Cancer stem cells; Epithelial-mesenchymal transition; Hyaluronan; Multidrug resistance; Tumor spheroid; Hyaluronic acid; biomaterial; breast cancer resistance protein; CD133 antigen; chitosan; gelatinase A; gelatinase B; Hermes antigen; hyaluronic acid; messenger RNA; multidrug resistance protein 1; nerve cell adhesion molecule; protein bcl 2; transcription factor NANOG; transcription factor Sox2; vimentin; artificial membrane; chitosan; hyaluronic acid; Article; cancer cell culture; cancer stem cell; cell invasion assay; cell migration assay; controlled study; epithelial mesenchymal transition; human; human cell; materials testing; non small cell lung cancer; phenotype; tumor spheroid; artificial membrane; batch cell culture; cancer stem cell; chemistry; epithelial mesenchymal transition; multicellular spheroid; pathology; physiology; procedures; synthesis; tumor cell line; tumor microenvironment; Batch Cell Culture Techniques; Biocompatible Materials; Cell Line, Tumor; Chitosan; Epithelial-Mesenchymal Transition; Humans; Hyaluronic Acid; Membranes, Artificial; Neoplastic Stem Cells; Phenotype; Spheroids, Cellular; Tumor Microenvironment |
顯示於: | 高分子科學與工程學研究所 |
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