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: Jun Won Park, Dong Min Park, Beom K Choi, Byoung S Kwon, Je Kyung Seong, Jeffrey E Green, Dae-Yong Kim, Hark Kyun Kim
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 54 Issue 11 Pg. 1521-7 (Nov 2015) ISSN: 1098-2744 [Electronic] United States
• PMID: 25307412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Cadherins
• Smad4 Protein
• Smad4 protein, mouse
• Tumor Suppressor Protein p53
• beta Catenin

Topics

• Adenocarcinoma (genetics)
• Animals
• Cadherins (genetics)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (genetics)
• Lung Neoplasms (genetics)
• Mice
• Mice, SCID
• Neoplasm Transplantation (methods)
• Smad4 Protein (genetics)
• Stomach Neoplasms (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Wnt Signaling Pathway (genetics)
• beta Catenin (genetics)