Cell proliferation, cell death, E-cadherin, metalloproteinase expression and angiogenesis in gastric cancer precursors and early cancer of the intestinal type

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

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Research on Function of Exosome of miR-328-3p Secreted by Bone Marrow Mesenchymal Stem Cells (BMSCs) on Restraining the Gastric Cancer Through Being Down-Regulated with Trefoil Factor 3

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2946 ◽

2022 ◽

Vol 12 (4) ◽

pp. 854-861

Author(s):

Jing Li ◽

Bo Xie ◽

Hu Wang ◽

Chengsong Chen ◽

Chengwu Pan ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Cell Proliferation ◽

Gastric Cancer Tissue ◽

Cancer Tissue ◽

Trefoil Factor ◽

Trefoil Factor 3 ◽

Marrow Mesenchymal Stem Cells ◽

Made In ◽

E Cadherin

Certain progress has been made in the therapeutic method against gastric cancer such as surgical operation combined with chemotherapy and radiation therapy in recent years. But the therapeutic efficacy and prognosis on gastric cancer was still not satisfactory. The function of exosome of miR-328–3p secreted by bone marrow stromal cells (BMSCs) on restraining the gastric cancer was studied in the present study. The BMSCs with highly-expressed miR-328-3p was established. The exosome in cell supernatant was collected. The exosome of BMSCs and MSCs with highlyexpressed miR-328-3p was added into SGC-7901 cells followed by analysis of miR-328-3p level by Real-time PCR and TFF3 (Trefoil Factor 3) level in exosome by Western blot, cell proliferation, expression of E-cadherin, Vimentin and Caspase-3. miR-328-39 expression was reduced and TFF3 was elevated in gastric cancer tissue (P < 0.05). miR-328-3p was upregulated and TFF3 was downregulated after addition of BMSCs exosomes along with increased cell proliferation and reduced E-cadherin and Caspase3 expression (P < 0.05). In conclusion, exosome of BMSCs could be regulated by miR-328-3p and TFF3 expression is restrained so as to regulate the biological behaviors of gastric cancer cell.

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Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

New Journal of Chemistry ◽

10.1039/c7nj00119c ◽

2017 ◽

Vol 41 (10) ◽

pp. 4087-4095

Author(s):

Jia Yu ◽

Xiaoqing Zhao ◽

Nanmengzi Zhang ◽

Chaoqun You ◽

Gang Yao ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cell Death ◽

Cancer Cells ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Cancer Cell Proliferation ◽

Gastric Cancer Cells ◽

Cell Death Pathway ◽

Gastric Cancer Cell Proliferation

Nine novel 3-nitroacridines were synthesized, of which 3 compounds inhibited gastric cancer cell proliferation via an autophagy-associated cell death pathway.

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Effect of dexmedetomidine on miR-144-3p expression and epithelial mesenchymal transition in gastric cancer cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i11.2 ◽

2021 ◽

Vol 20 (11) ◽

pp. 2249-2253

Author(s):

Zong Chen ◽

Yong Ding ◽

Ying Zeng ◽

Zhifeng Chen ◽

Xueping Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Control Group ◽

Gastric Cancer Cells ◽

Rat Cardiomyocytes ◽

Mesenchymal Transition ◽

Geo Database ◽

E Cadherin

Purpose: To investigate the effect of dexmedetomidine (DEX) on epithelial mesenchymal transition (EMT) in gastric cancer cells, and the role of microRNA-144-3p (miR-144-3p) in the process.Methods: The effect of DEX on miRNA expression profile was analyzed using GEO database(https://www.ncbi.nlm.nih.gov/gds/). Human gastric cancer cells were cultured in vitro, and one group of cells was treated with saline for 48 h (control group). Cells treated with DEX at doses of 0.01, 0.1 and 1.0 μmol/L for 48 h were marked as low-, medium- and high-DEX concentration groups. The mRNA expression levels of miR-144-3p, ZEB1, E-cadherin and vimentin were determined using real-time quantitative polymerase chain reaction (RT-PCR), while the protein expressions of ZEB1, E-cadherin and vimentin were assayed with Western blotting. Cell proliferation was determined with CCK-8 assay, while metastasis was measured using Transwell assay.Results: The GEO database demonstrated that the expression of miR-144-3p in rat cardiomyocytes was significantly decreased after DEX treatment (p < 0.05). The expression of miR-144-3p was decreased in all groups, when compared to the control group, but the expressions of ZEB1 and vimentin were increased, while that of E-cadherin was down-regulated (p < 0.05). Cell proliferation in the high-DEX concentration group was decreased (p < 0.05). The degrees of cell invasion and migration were increased in the medium- and high-DEX concentration groups (p < 0.05).Conclusion: DEX promotes the metastasis of gastric cancer cells by regulation of epithelialmesenchymal transition (EMT) and the expression of miR-144-3p. This finding provides a new insight into the treatment of gastric cancer.

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Digital PCR identifies changes in CDH1 (E-cadherin) transcription pattern in intestinal-type gastric cancer

Oncotarget ◽

10.18632/oncotarget.13401 ◽

2016 ◽

Vol 8 (12) ◽

pp. 18811-18820 ◽

Cited By ~ 3

Author(s):

Raefa Abou Khouzam ◽

Chiara Molinari ◽

Samanta Salvi ◽

Monica Marabelli ◽

Valeria Molinaro ◽

...

Keyword(s):

Gastric Cancer ◽

Digital Pcr ◽

Intestinal Type ◽

Transcription Pattern ◽

E Cadherin

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Correlation between the expression abnormalities of E-cadherin-β-catenin complex and lymph node metastasis (LNM) in early gastric cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15105 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15105-15105

Author(s):

T. Yoshii ◽

Y. Miyagi ◽

Y. Nakamura ◽

O. Motohashi ◽

K. Nishimura ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Primary Lesion ◽

Clinicopathological Features ◽

Intestinal Type ◽

Group 14 ◽

Junctional Structure ◽

E Cadherin ◽

Cell Cell

15105 Background: Therapy for early gastric cancer (GC) varies according to risk of LNM. When the possibility of LNM is very remote, the primary lesion can be resected by the minimally invasive endoscopic surgery only. Therefore, useful parameters predicting LNM are needed. E-cadherin, a component of the cell-cell junctional structure, is known to correlate with GC. In vitro, previous studies elucidated that disorders of cell-cell junction increased the potential of metastasis, and that phosphorylation of β-catenin by c-erbB-2 induced loss of membranous E-cadherin and β-catenin, resulting in junctional structure disorders. Here we evaluated significance of analysis of these molecules in LNM prediction in early GC. Methods: The clinicopathological features and immunohistochemical expressions of E-cadherin, β-catenin, and c-erbB-2 in the primary lesion were studied in 28 patients (LNM +ve group: 14, LNM1 -ve group: 14) selected from 272 patients who underwent radical surgery for early GC between April 2000 to March 2004 at our hospital. All the patients consented to use of their stomach tissues for the clinical study afterwards. Statistical analysis was performed by t-test or χ2 test. Results: The clinicopathological features showed no significant differences between both groups. Loss of the membranous E-cadherin was noticed in 12 (85%) of the 14 LNM +ve patients, and in 8 (57%) of the 14 LNM -ve patients (p=0.209). This result was more remarkable in the intestinal type GC as the corresponding figures were 83% (5 of 6 ) and 16% (1 of 6) (p=0.083), respectively. Loss of the membranous β-catenin also showed a remarkable similar trend in the intestinal type GC, and the corresponding figures were 100% (6 of 6) and 50% (3 of 6) (p=0.182), respectively. Two patients showed over-expression of c-erbB2 and nuclear accumulation of β-catenin, and both had intestinal type GC with LNM. Conclusions: These results suggested that the same molecular signal pathway - as in vitro - including E-cadherin, β-catenin, and c-erbB2 induced LNM in early GC (intestinal type). We concluded that analysis of the expressions of these molecules is useful for not only LNM prediction but also determination of the therapeutic modality especially in intestinal type early GC. No significant financial relationships to disclose.

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SUZ12 promotes gastric cancer cell proliferation and metastasis by regulating KLF2 and E-cadherin

Tumor Biology ◽

10.1007/s13277-015-3195-7 ◽

2015 ◽

Vol 36 (7) ◽

pp. 5341-5351 ◽

Cited By ~ 28

Author(s):

Rui Xia ◽

Fei-yan Jin ◽

Kai Lu ◽

Li Wan ◽

Min Xie ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Cancer Cell Proliferation ◽

Proliferation And Metastasis ◽

Gastric Cancer Cell Proliferation ◽

Cell Proliferation And Metastasis ◽

E Cadherin

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Increased Epithelial Cadherin Expression among Japanese Intestinal-Type Gastric Cancers Compared with Specimens from American Patients of European Descent

The American Surgeon ◽

10.1177/000313480607200412 ◽

2006 ◽

Vol 72 (4) ◽

pp. 332-338 ◽

Cited By ~ 1

Author(s):

Charles P. Theuer ◽

Rasha Al-Kuran ◽

Yoshiyuki Akiyama ◽

Minoru Okumura ◽

Al Ziogas ◽

...

Keyword(s):

Gastric Cancer ◽

Gastroesophageal Junction ◽

Far East ◽

The United States ◽

Intestinal Type ◽

Malignant Cells ◽

European Descent ◽

Epithelial Cadherin ◽

The Far East ◽

E Cadherin

The different patterns of gastric cancer in the Far East and West have evolved to the extent that it has been suggested that the disease in Japan is biologically less aggressive than in the West. We studied paraffin-embedded, formalin-fixed tissue blocks from Japanese patients and American patients of European descent who had undergone gastrectomy for gastric cancer not involving the gastroesophageal junction. Specimens were staged (T stage), graded (Lauren classification), and biomarker expression (epithelial cadherin [E-cadherin], c-erbB2, Ki67, and p53) was quantified using immunohistochemistry without knowledge of the country of origin. E-cadherin was expressed in 49 per cent of malignant cells from Japanese specimens compared with 27 per cent of malignant cells from American specimens (P = 0.04). The expression of E-cadherin on diffuse cancers from the two countries was similar (34.4 in Japanese vs 41.5 in American, P = 0.92). E-cadherin expression, however, was significantly higher among intestinal cancers from the two countries: 56.3 per cent of cells from intestinal or mixed cancers from Japan (n = 32) expressed E-cadherin compared with 22.2 per cent of American specimens (n = 12; P = 0.008). c-erbB2 was expressed on a higher proportion of malignant cells from American specimens (30% vs 22%; P = 0.20). E-cadherin expression, a favorable prognostic factor, is more common in Japanese intestinal-type gastric cancer not involving the gastroesophageal junction. If the biology of gastric cancer in the Far East is less aggressive than that in the United States, it is likely that treatments need to be individualized.

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Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial–mesenchymal transition in gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819827697 ◽

2019 ◽

Vol 12 ◽

pp. 175628481982769 ◽

Cited By ~ 9

Author(s):

Kecheng Zhang ◽

Canrong Lu ◽

Xiaohui Huang ◽

Jianxin Cui ◽

Jiyang Li ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Tumor Cell ◽

Epithelial Mesenchymal Transition ◽

Negative Control ◽

Tumor Cell Proliferation ◽

Mesenchymal Transition ◽

E Cadherin

Background: The clinical relevance and biological role of tissular AOC4P in gastric cancer (GC) remains to be clarified. Methods: The association between AOC4P expression and clinicopathological characteristics was investigated. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of AOC4P on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. In vivo, animal experiments were conducted to confirm the in vitro findings. Quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence were used to investigate the potential mechanisms. Results: Expression levels of AOC4P were significantly higher in tumor tissues than in noncancerous tissues, and patients with high levels of AOC4P had poor overall and disease-free survival. AOC4P expression was correlated with lymphovascular invasion. In vitro, knockdown of AOC4P inhibited tumor cell proliferation, migration, and invasion, and promoted apoptosis of MGC-803 and BGC-823 cells. In vivo, BGC-823 cells transfected with AOC4P siRNA formed smaller and lighter tumors than BGC-823 cells transfected with negative control siRNA in severe combined immunodeficiency mice. Additionally, the si- AOC4P group had less proliferating cells and more apoptotic cells in tumor xenografts compared with the negative control. Mechanistically, knockdown of AOC4P decreased the expression of vimentin and MMP9, while increasing the expression of E-cadherin. Immunofluorescence confirmed the relationship between AOC4P expression and E-cadherin, vimentin, and MMP9 levels in clinical GC specimens. Conclusions: AOC4P promotes tumorigenesis and progression partly through epithelial–mesenchymal transition in GC. Additionally, AOC4P may serve as a prognostic biomarker for clinical decision making.

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