title: Probing the Bi-directional Interaction Between Microglia and Gliomas in a Tumor Microenvironment on a Microdevice.
abstract: It has been proven that microglia are involved in both early and late stages of glioma progression and contribute substantially to the tumor mass of gliomas. Because no appropriate in vitro or in vivo investigative approach is available, the dynamic interaction between microglia and gliomas during tumor formation remains unclear. In this study, three types of microfluidic assay were developed to examine the outcomes of the dynamic interaction between microglia and gliomas. Co-migration assay and two-dimensional cell co-culture assay have been used to show that microglial BV-2 cells migrate toward C6 glioma cells and inhibit tumor growth during the early stage of tumorigenesis. However, in three-dimensional cell spheres (three-dimensional cell co-culture assay) that contain a large amount of glioma cells, mimicking the late stage of glioma growth, the phagocytosis of microglia was suppressed, which suggests that glioma cells could reeducate classically activated microglia into a tumor-promoting state at some point during tumor progression. Notably, we found that microglia could contribute to tumor invasion and acquisition of the epithelial-mesenchymal transition phenotype in the glioma microenvironment during the early stage and the late stage of tumor progression. In conclusion, we have developed a potential quantitative method for in vitro study of glioma immunity and provided evidence for the duality of glioma-associated microglia.
authors.affiliation: Department of Physiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.|Center Laboratory Department, General Hospital of Chengdu Army, Chengdu, 610083, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gu
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457, Zhongshan Road, Dalian, 116023, China.|State key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110016, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.|Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457, Zhongshan Road, Dalian, 116023, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tao
authors.affiliation: State key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110016, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Yu
authors.affiliation: State key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110016, China.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Physiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Physiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China. li.ap@126.com.
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457, Zhongshan Road, Dalian, 116023, China. jhqin@dicp.ac.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qin
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D051381:Rats; D059016:Tumor Microenvironment / Q000502:physiology*
keywords: Epithelial-mesenchymal transition; Glioma; Microfluidic device; Microglia; Migration; Phagocytosis