title: Establishment and characterization of metastatic gastric cancer cell lines from murine gastric adenocarcinoma lacking Smad4, p53, and E-cadherin.
abstract: There is a strong need for murine gastric cancer cell line models recapitulating human gastric cancers. Here, we describe two murine gastric cancer cell lines designated as NCC-S1 and NCC-S3. They were generated from gastric adenocarcinomas that formed in a Villin-cre, Smad4(F/F) , Trp53(F/F) , Cdh1(F/wt) mouse and a Pdx1-cre, Trp53(F/F) , Cdh1(F/F) mouse, respectively. Molecular profiles of both cell lines were very similar to human gastric cancer. NCC-S1M and NCC-S3M subpopulation clones were isolated from pulmonary metastasis of heterotopic allografts of NCC-S1 and NCC-S3 cells, respectively. NCC-S1M and NCC-S3M showed enhanced in vivo growth rates and metastatic potentials and exhibited epithelial-to-mesenchymal transition features. NCC-S1M cells developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner, and were useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB antibody. NCC-S1M and NCC-S3M cells demonstrated Wnt/β-catenin pathway activation, and knockdown of Ctnnb1 reversed the metastatic phenotype of NCC-S1M. These results underscore the role of Wnt/β-catenin pathway in metastatic phenotype of gastric cancer. Taken together, our novel metastatic gastric cancer cell lines are useful resources for drug development and metastasis research.
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Park
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Beom K
authors.initials: BK
authors.lastname: Choi
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
authors.affiliation: College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Green
authors.affiliation: College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods; D051901:Smad4 Protein / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D015820:Cadherins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin
keywords: EMT; cell line; gastric cancer; mouse; β-catenin pathway