title: Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells.
abstract: 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 the in vivo tumor 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 greater in vitro invasion 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.
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Sun
authors.affiliation: College of Life Science &Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|School of Life Science, Dalian University, Dalian, 116023, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|Dalian Municipal Central Hospital, Dalian, 116033, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
mesh_terms: D000464:Alginates / Q000737:chemistry; D032701:Biomimetics; D002118:Calcium / Q000737:chemistry; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D002809:Chondroitin Sulfates; D002118:Calcium