title: Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells.
abstract: Gastric cancer (GC) is a common aggressive malignant tumor with high incidence and mortality worldwide. GC is classified into intestinal and diffuse types according to the histo-morphological features. Because of distinctly different clinico-pathological features, new cancer therapy strategies and in vitro preclinical models for the two pathological variants of GC is necessary. Since extracellular matrix (ECM) influence the biological behavior of tumor cells, we hypothesized that GC might be more similarly modeled in 3D with matrix rather than in 2D. Herein, we developed a microfluidic-based a three-dimensional (3D) in vitro gastric cancer model, with subsequent drug resistance assay. AGS (intestinal type) and Hs746T (diffuse type) gastric cancer cell lines were encapsulated in collagen beads with high cellular viability. AGS exhibited an aggregation pattern with expansive growth, whereas Hs746T showed single-cell-level infiltration. Importantly, in microtumor models, epithelial-mesenchymal transition (EMT) and metastatic genes were upregulated, whereas E-cadherin was downregulated. Expression of ß-catenin was decreased in drug-resistant cells, and chemosensitivity toward the anticancer drug (5-FU) was observed in microtumors. These results suggest that in vitro microtumor models may represent a biologically relevant platform for studying gastric cancer cell biology and tumorigenesis, and for accelerating the development of novel therapeutic targets.
authors.affiliation: KAIST, Department of Bio and Brain Engineering, Daejeon 34141, Republic of Korea.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Jang
authors.affiliation: KAIST, Department of Bio and Brain Engineering, Daejeon 34141, Republic of Korea.
authors.forename: Ilkyoo
authors.initials: I
authors.lastname: Koh
authors.affiliation: Department of Nano Bio Research, National NanoFab Center, Daejeon 34141, Republic of Korea.
authors.forename: Seok Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Yonsei University College of Medicine, Department of Surgery, Seoul 03722, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: KAIST, Department of Bio and Brain Engineering, Daejeon 34141, Republic of Korea.
authors.forename: Pilnam
authors.initials: P
authors.lastname: Kim
mesh_terms: D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D046210:Microfluidic Analytical Techniques; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin