scholarly journals CD44s Assembles Hyaluronan Coat on Filopodia and Extracellular Vesicles and Induces Tumorigenicity of MKN74 Gastric Carcinoma Cells

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 276 ◽  
Author(s):  
Kai Härkönen ◽  
Sanna Oikari ◽  
Heikki Kyykallio ◽  
Janne Capra ◽  
Sini Hakkola ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Binding Capacity ◽  
Standard Form ◽  
Cellular Functions ◽  
Gastric Cancer Cells ◽  
Gastric Carcinoma Cell ◽  
Proliferation Capacity ◽  
Cd44s Expression

CD44 is a multifunctional adhesion molecule typically upregulated in malignant, inflamed and injured tissues. Due to its ability to bind multiple ligands present in the tumor microenvironment, it promotes multiple cellular functions related to tumorigenesis. Recent data has shown that CD44 and its principal ligand hyaluronan (HA) are carried by extracellular vesicles (EV) derived from stem and tumor cells, but the role of CD44 in EV shedding has not been studied so far. To answer this question, we utilized CD44-negative human gastric carcinoma cell line MKN74 manipulated to stably express CD44 standard form (CD44s). The effect of CD44s expression on HA metabolism, EV secretion, morphology and growth of these cells was studied. Interestingly, HAS2 and HYAL2 expression levels were significantly upregulated in CD44s-expressing cells. Cell-associated HA levels were significantly increased, while HA levels in the culture medium of CD44s-positive cells was lower compared to CD44s-negative MOCK cells. CD44s expression had no significant effect on the proliferation capacity of cells, but cells showed diminished contact inhibition. Superresolution imaging revealed that CD44s and HA were accumulated on filopodia and EVs secreted from CD44s-positive cells, but no differences in total numbers of secreted EV between CD44s-negative and -positive cells was detected. In 3D cultures, CD44s-expressing cells had an enhanced invasion capacity in BME gel and increased spheroidal growth when cultured in collagen I gel. No significant differences in mitotic activity, tumor size or morphology were detected in CAM assays. However, a significant increase in HA staining coverage was detected in CD44s-positive tumors. Interestingly, CD44s-positive EVs embedded in HA-rich matrix were detected in the stromal areas of tumors. The results indicate that CD44s expression significantly increases the HA binding capacity of gastric cancer cells, while the secreted HA is downregulated. CD44s is also carried by EVs secreted by CD44s-expressing cells. These findings highlight the potential usefulness of CD44s and its ligands as multipurpose EV biomarkers, because they are upregulated in inflammatory, injured, and cancer cells and accumulate on the surface of EVs secreted in these situations.

Chrysin Alters microRNAs Expression Levels in Gastric Cancer Cells: Possible Molecular Mechanism

Drug Research ◽  
2017 ◽  
Vol 67 (09) ◽  
pp. 509-514 ◽  
Author(s):  
Farideh Mohammadian ◽  
Younes Pilehvar-Soltanahmadi ◽  
Shahriar Alipour ◽  
Mehdi Dadashpour ◽  
Nosratollah Zarghami
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Gastric Carcinoma Cell ◽  
Expression Levels ◽  
Mirnas Expression ◽  
Chemopreventive Activity

Abstract Background Gastric carcinoma still remains the second most common cause of cancer mortality in the world. Chrysin, as a flavone, has showed cancer chemopreventive activity. The cellular and molecular mechanisms of chrysin in cancer cells have not been fully understood. Objective In this study, we investigate expression levels of let-7a, miR-9, mir-18a, miR-21, miR-22, miR-34a, miR-126 and mir-221 to describe the anti-cancer effects of chrysin. Materials and Methods The cytotoxic effects of chrysin were assessed using MTT assay. The effect of chrysin on the microRNAs expression was determined by qRT-PCR. Results The MTT results for different concentrations of chrysin at different times on the Gastric carcinoma cells showed that IC50 for chrysin was 68.24 µM after 24 h of treatment. Expression analysis identified that miR-18, miR-21 and miR-221 were down regulated whereas let-7a, miR-9, miR-22, miR-34a and miR-126 were up regulated in Gastric carcinoma cell line (p<0.05). Conclusion Treatment with chrysin can alter the miRNAs expression and these findings might be an explanation for molecular mechanism of chrysin effect on gastric cancer.

Antitumorigenic effect of plumbagin by induction of SHP1 in human gastric carcinoma cell lines.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 74-74
Author(s):  
Jin Sung Koh ◽  
Jong-Jae Park ◽  
Moon Kyung Joo ◽  
Hyo Soon Yoo ◽  
Jiwon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastric Carcinoma Cell ◽  
Stat3 Pathway

74 Background: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-drived natural agent extracted from the root of Plumbago zeylanic. A recent study reported that plumbagin down-regulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various anti-tumor effects. We aimed in this in vitrostudy to demonstrate the inhibition of JAK2-STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in gastric cancer cell line. Methods: We performed Wetern blot to measure SHP1, phospho-JAK2/STAT3 level, and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate target gene expression of STAT3. Several functional studies such as water soluble tetrazolium-1 (WST-1) assay, wound closure assay and matrigel invasion assay were also performed. Results: Plumbagin induced SHP1 expression and simultaneously down-regulated phospho-JAK2/STAT3 level via dose-and time-dependant manner in MKN28 cell, a gastric carcinoma cell line which has negative SHP1 expression. This effect was consistent when JAK2-STAT3 signaling was activated by interleukin-6, and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, VEGF1, survivin, MMP9, known target products of STAT3 activation in gastric cancinogenesis. The functional effect of plumbagin could be validated as inhibition of cell proliferation, migration and invasion, which are the results of activation of JAK2-STAT3 pathway in gastric cancer cells. Conclusions: Plumbagin is a potential negative regulator of cellular growth, migration and invasion by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.

Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

PROTEOMICS ◽  
2021 ◽  
pp. 2000098
Author(s):  
Annalisa L.E. Carli ◽  
Shoukat Afshar‐Sterle ◽  
Alin Rai ◽  
Haoyun Fang ◽  
Ryan O'Keefe ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Stem Cell Marker ◽  
Cancer Stem Cell Marker ◽  
Cell Marker ◽  
Gastric Cancer Cells ◽  
Migratory Phenotype

scholarly journals Expression of miR-634 in gastric carcinoma and its effects on proliferation, migration, and invasion of gastric cancer cells

2018 ◽  
Vol 7 (3) ◽  
pp. 776-787 ◽  
Author(s):  
Jiao Guo ◽  
Chun-Dong Zhang ◽  
Jia-Xiang An ◽  
Yun-Yun Xiao ◽  
Shuai Shao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gastric Cancer Cells

HOXB5 induces invasion and migration through direct transcriptional up-regulation of β-catenin in human gastric carcinoma

2015 ◽  
Vol 472 (3) ◽  
pp. 393-403 ◽  
Author(s):  
Chang-Soo Hong ◽  
Oh Jeong ◽  
Zhengri Piao ◽  
Chen Guo ◽  
Mi-Ran Jung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Transcriptional Expression ◽  
Gastric Cancer Cells ◽  
Migration Activity ◽  
Invasion And Migration ◽  
Human Gastric Carcinoma ◽  
And Migration

HOXB5 is significantly up-regulated in gastric cancer and its expression is closely correlated with β-catenin expression. HOXB5 binds directly to the CTNNB1 promoter and activates its transcriptional expression, which in turn promotes invasion and migration activity of gastric cancer cells.

scholarly journals Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Atene Ito ◽  
Shunsuke Kagawa ◽  
Shuichi Sakamoto ◽  
Kazuya Kuwada ◽  
Hiroki Kajioka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ascitic Fluid ◽  
Extracellular Vesicles ◽  
Peritoneal Cavity ◽  
Peritoneal Dissemination ◽  
Tumor Associated Macrophages ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Patients

Abstract Background Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated. Methods The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored. Results Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein. Conclusion EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.

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