title: GAGE12 mediates human gastric carcinoma growth and metastasis.
abstract: The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Medical Center and Sungkyunkwan University, Seoul, Korea; Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center and Sungkyunkwan University, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Song
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Chae
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Kang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; C113434:GAGE7 protein, human; D009363:Neoplasm Proteins
keywords: EMT; GAGE; Krukenberg; MET; animal model; gastric carcinoma; metastasis; orthotopic; ovary; stomach