title: Establishment of a gastric cancer subline with high metastatic potential using a novel microfluidic system.
abstract: Metastasis is an important hallmark of malignant tumors. In this study, we developed a microfluidic system to screen highly metastatic sublines via differential resolution of cell invasiveness. The system was composed of a PDMS-glass device connected with a syringe pump and a Petri dish. To facilitate the selection process, a long-term cell invasion driving force based on a chemotactic factor gradient was created using the Petri dish-based liquid supply pattern, and the invasive cells were collected for round-by-round selection via an open region in the chip. Using the system, we established an SGC-7901/B2 subline from the human gastric cancer SGC-7901 cell line by only two rounds of selection. In vitro assays showed that the SGC-7901/B2 cells were superior to the parental cells in proliferation and invasiveness. Furthermore, an in vivo tumorigenicity assay demonstrated that compared with the parental cells, the subline had stronger spontaneous metastatic and proliferative capability, which led to a shorter survival duration. Additionally, the protein expression differences including E-cadherin and Smad3 between the subline and parental cells were revealed. In conclusion, this microfluidic system is a highly effective tool for selecting highly metastatic sublines, and SGC-7901/B2 cells could serve as a potential model for tumor metastasis research.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Zhe-Zhou
authors.initials: ZZ
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Wan-Ming
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Mathematics, China Medical University, Shenyang 110122, PR China.
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Shan
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: De-Zheng
authors.initials: DZ
authors.lastname: Yuan
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018703:Founder Effect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056656:Lab-On-A-Chip Devices; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C497790:SMAD3 protein, human; D051900:Smad3 Protein