Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer

Kanda, Mitsuro; Shimizu, Dai; Tanaka, Haruyoshi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Takami, Hideki; Niwa, Yasumasa; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Kodera, Yasuhiro

doi:10.1002/bjs.10876

Cited by 46 publications

(45 citation statements)

References 32 publications

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“…This enables us to use these cell lines properly according to the purpose of the animal experiment by applying several characteristics, such as cell differentiation and molecular expression. These findings contributed to our previous studies of the identification of molecules related to the formation of peritoneal and hepatic metastasis (35,36).…”

Section: Peritoneal Metastasis Formation In Nude Mice After Intraperisupporting

confidence: 73%

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Miwa

Kanda

Umeda

et al. 2019

In Vivo

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Background/Aim: Establishment of mouse xenograft models is necessary for oncological research and depends on the characteristics of the cell lines and the immune system of the host. In this study, we describe the development of mouse xenograft models using human gastric cancer (GC) cell lines. Materials and Methods: MKN1 stably-expressing luciferase (MKN1-Luc), N87, KATO III, MKN45 stably-expressing luciferase (MKN45-Luc), NUGC4, and OCUM-1 human GC cell lines were injected intraperitoneally into mice to establish peritoneal metastasis models. MKN45-Luc were injected into subcutaneously implanted spleen, and MKN1-Luc and MKN45-Luc were injected directly into the portal veins of mice for the establishment of hepatic metastasis models. Results: Peritoneal metastasis was formed after implantation of MKN1-Luc, N87, KATO III, MKN45-Luc, and NUGC4 in nude mice, but not formed in OCUM-1 even in NOD/SCID mice. After intrasplenic injection of MKN45-Luc, we found no hepatic metastasis formation. We identified hepatic metastasis formation after direct injection of MKN45-Luc and MKN1-Luc into the portal veins of NOD/SCID mice. Conclusion: Peritoneal and hepatic metastasis mouse xenograft models were successfully established using several human GC cell lines. Gastric cancer (GC) is the fourth leading cause of cancerrelated death worldwide (1). Perioperative adjuvant therapy has improved prognosis to a certain degree (2-4). However, Materials and Methods Cell lines and cell culture. MKN1 cells stably expressing luciferase (MKN1-Luc), MKN45 cells stably expressing luciferase (MKN45-Luc), NUGC4, and OCUM-1 were obtained from the Japanese Collection of Research Bio Resources Cell Bank (JCRB) (Osaka, Japan). N87 and KATO III cell lines were purchased from the American Type Culture Collection (ATCC; Manassas, VA, USA). Cells were incubated at 37˚C with 5% CO 2 in the recommended medium supplemented with 10% fetal bovine serum. The characteristics of the gastric cancer cell lines are listed in Table I.

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Section: Peritoneal Metastasis Formation In Nude Mice After Intraperisupporting

confidence: 73%

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Miwa

Kanda

Umeda

et al. 2019

In Vivo

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“…The level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was determined as an internal standard, and the expression level of each sample was calculated as the value of MAGEA6 mRNA divided by that of GAPDH mRNA (16). The expression levels of 84 key genes was analyzed using the Human Epithelial to Mesenchymal Transition (EMT) RT Profiler PCR Array (Qiagen, Hilden, Germany) (17,18).…”

Section: Sample Collectionmentioning

confidence: 99%

Tissue Expression of Melanoma-associated Antigen A6 and Clinical Characteristics of Gastric Cancer

et al. 2019

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Background: Gastric cancer (GC) exhibits heterogeneous clinical and molecular features, requiring the development of new biomarkers to further understand this disease. Our transcriptomic analysis detected overexpression of melanoma-associated antigen A6 (MAGEA6) in metastatic GC, leading us to determine the clinical significance of MAGEA6 in GC. Materials and Methods: Fourteen GC cell lines and 230 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. Polymerase chain reaction array analysis was performed to identify coordinately expressed cancer-related genes, and immunohistochemistry (IHC) was used to detected MAGEA6 expression in situ. Results: MAGEA6 mRNA levels were positively correlated with the expression of matrix metallopeptidase 9 mRNA. MAGEA6 mRNA levels were higher in GC tissues compared with those in normal adjacent tissues. Patients with high MAGEA6 expression had significantly worse prognosis. MAGEA6 protein levels in primary lesions predicted the likelihood of recurrence. Conclusion: Overexpression of MAGEA6 in GC tissues represents a promising biomarker for assessing the malignant phenotype of GC. Gastric cancer (GC) is the third leading cause of cancerrelated death worldwide (1). GC is difficult to treat because 5903 This article is freely accessible online.

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“…Recently, Kanda et al identified SYT7 to be a novel molecule that promoted hepatic metastasis of gastric cancer [21]. Increased expression of SYT13 is significantly associated with an increased risk of peritoneal recurrence in patients with gastric cancer, and down-regulation of SYT13 inhibited migration and invasion of gastric cancer cells in vitro [22]. The findings from the present study support these previous studies, which showed that SYT12 expression significantly promoted the migration and invasion of LUAD cells ( Figure 3A-3D).…”

Section: Discussionmentioning

confidence: 99%

Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

et al. 2020

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Background: This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD. Material/Methods: Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD. Results: SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors. Conclusions: Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.

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Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer

Abstract: SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.

Cited by 46 publications

References 32 publications

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Tissue Expression of Melanoma-associated Antigen A6 and Clinical Characteristics of Gastric Cancer

Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

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