scholarly journals S100P is a molecular determinant of E-cadherin function in gastric cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Joana Figueiredo ◽  
Rita Barros ◽  
Patrícia Oliveira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Data Mining Approach ◽  
Molecular Determinant ◽  
Gastric Cancer Patients ◽  
And Function ◽  
E Cadherin

Abstract Background E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad− tumours, despite not being significantly associated with overall survival on its own. Conclusions We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies. Graphical abstract

scholarly journals Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xing Kang ◽  
En Xu ◽  
Xingzhou Wang ◽  
Lulu Qian ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Vasculogenic Mimicry ◽  
Gastric Cancer Tissue ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Tenascin C ◽  
Gastric Cancer Patients

AbstractGastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

scholarly journals ELISA study of matrix metalloproteinases 2, 7, 9 and their type 2 tissue inhibitor in the tumors of gastric cancer patients: clinical and pathologic correlations

2018 ◽  
Vol 46 (4) ◽  
pp. 323-329
Author(s):  
E. S. Gershtein ◽  
A. A. Ivannikov ◽  
V. L. Chang ◽  
N. A. Ognerubov ◽  
М. M. Davydov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Patients

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.

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

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.

scholarly journals HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marta Smolińska ◽  
Dariusz Grzanka ◽  
Paulina Antosik ◽  
Anna Kasperska ◽  
Izabela Neska-Długosz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Statistical Significance ◽  
Expression Patterns ◽  
Clinical Information ◽  
Tissue Microarrays ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Satb1 Expression

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Yu Jin Kim ◽  
Won Shik Kim ◽  
Sang Woo Kim ◽  
Woon Yong Jung
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Gastric Adenoma ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Gastric Cancer Patients ◽  
And Function

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

scholarly journals Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia

2005 ◽  
Vol 42 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Nora Manoukian Forones ◽  
Ana Paula Souza Carvalho ◽  
Oswaldo Giannotti-Filho ◽  
Laércio Gomes Lourenço ◽  
Celina Tizuko Fujiyama Oshima
Keyword(s):  
Gastric Cancer ◽  
Intestinal Metaplasia ◽  
Stage Iv ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Advanced Stage ◽  
Two Samples ◽  
Significant Difference ◽  
Proliferation And Apoptosis ◽  
Gastric Cancer Patients

BACKGROUND: Higher proliferation is commonly observed in cancer cells. Apoptosis can be a useful measure of a tumor cell kinetic. Alteration of the balance between proliferation and apoptosis is associated with cancer. AIM: To study proliferation and apoptosis on gastric cancer and in intestinal metaplasia. METHODOLOGY: Twenty-two samples from gastric adenocarcinomas and 22 biopsies from intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin slides and the expression of p53, bcl-2 and Ki67 were determined by immunohistochemistry. RESULTS: The number of the apoptotic cells was higher in cancer. Ki 67LI increased from intestinal metaplasia to gastric cancer. p53 was positive in 68% of the patients with cancer, more frequently in advanced stage and negative in samples of intestinal metaplasia. Although there was no significant difference between the groups, bcl-2 was positive in 45% of gastric cancer tissue and in 68% of metaplasia. In gastric cancer patients bcl-2 was expressed in early gastric cancer more frequently than in advanced stage. CONCLUSION: The positivity of bcl-2 was higher in metaplasia and probably is involved in the progression of carcinogenesis. p53 was negative in metaplasia and positive in more than half of the gastric cancer, mostly in stage IV, suggesting a late event in gastric cancer.

scholarly journals Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Beibei Chen ◽  
Sai-Qi Wang ◽  
Jinxi Huang ◽  
Weifeng Xu ◽  
Huifang Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
And Migration ◽  
Induced Apoptosis ◽  
Gastric Cancer Patients

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

scholarly journals Gastrin Vaccine Alone and in Combination With an Immune Checkpoint Antibody Inhibits Growth and Metastases of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jill P. Smith ◽  
Hong Cao ◽  
Wenqiang Chen ◽  
Kanwal Mahmood ◽  
Teresa Phillips ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Receptor Expression ◽  
Tissue Array ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

Gastric cancer is a leading cause of cancer-related deaths worldwide. Recently, clinical studies have demonstrated that many of those with advanced gastric cancer are responsive to immune checkpoint antibody therapy, although the median survival even with these new agents is less than 12 months for advanced disease. The gastrointestinal peptide gastrin has been shown to stimulate growth of gastric cancer in a paracrine and autocrine fashion through the cholecystokinin-B receptor (CCK-BR), a receptor that is expressed in at least 56.6% of human gastric cancers. In the current investigation, we studied the role of the gastrin-CCK-BR pathway in vitro and in vivo as well as the expression of the CCK-BR in a human gastric cancer tissue array. CCK-BR and PD-L1 receptor expression and gastrin peptide was found in two murine gastric cancer cells (NCC-S1 and YTN-16) by qRT-PCR and immunocytochemistry. Treatment of NCC-S1 cells with gastrin resulted in increased growth. In vivo, the effects of a cancer vaccine that targets gastrin peptide (polyclonal antibody stimulator—PAS) alone or in combination with a Programed Death-1 antibody (PD-1 Ab) was evaluated in immune competent mice (N = 40) bearing YTN-16 gastric tumors. Mice were treated with PBS, PD-1 Ab (50 µg), PAS (250 µg), or the combination of PD-1 Ab with PAS. Tumor growth was significantly slower than controls in PAS-treated mice, and tumor growth was decreased even more in combination-treated mice. There were no metastases in any of the mice treated with PAS either alone or in combination with PD-1 Ab. Tumor proliferation by the Ki67 staining was significantly decreased in mice treated with PAS monotherapy or the combination therapy. PAS monotherapy or combined with PD-1 Ab increased tumor CD8+ T-lymphocytes and decreased the number of immunosuppressive M2-polarized tumor-associated macrophages. CCK-BR expression was identified in samples from a human tissue array by immunohistochemistry confirming the clinical relevance of this study. These results confirm the significance of the gastrin-CCK-BR signaling pathway in gastric cancer and suggest that the addition of a gastrin vaccine, PAS, to therapy with an immune checkpoint antibody may decrease growth and metastases of gastric cancer by altering the tumor microenvironment.

scholarly journals Upregulation of long noncoding RNA SNHG1 indicates a poor prognosis in patients with gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Expression Levels

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.

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