scholarly journals Continuous Long-Term Exposure to Low Concentrations of MWCNTs Induces an Epithelial-Mesenchymal Transition in BEAS-2B Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1742
Author(s):  
Hélène Barthel ◽  
Christian Darne ◽  
Laurent Gaté ◽  
Athanase Visvikis ◽  
Carole Seidel
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Pulmonary Exposure ◽  
Adverse Health Effects ◽  
Low Concentrations ◽  
Mitotic Abnormalities ◽  
Epithelial Marker ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

In the field of nanotechnology, the use of multi-walled carbon nanotubes (MWCNTs) is growing. Pulmonary exposure during their production, use, and handling is raising concerns about their potential adverse health effects. The purpose of this study is to assess how the physical characteristics of MWCNTs, such as diameter and/or length, can play a role in cellular toxicity. Our experimental design is based on the treatment of human bronchial epithelial cells (BEAS-2B) for six weeks with low concentrations (0.125–1 µg/cm2) of MWCNTs having opposite characteristics: NM-403 and Mitsui-7. Following treatment with both MWCNTs, we observed an increase in mitotic abnormalities and micronucleus-positive cells. The cytotoxic effect was delayed in cells treated with NM-403 compared to Mitsui-7. After 4–6 weeks of treatment, a clear cellular morphological change from epithelial to fibroblast-like phenotype was noted, together with a change in the cell population composition. BEAS-2B cells underwent a conversion from the epithelial to mesenchymal state as we observed a decrease in the epithelial marker E-cadherin and an increased expression of mesenchymal markers N-cadherin, Vimentin, and Fibronectin. After four weeks of recovery, we showed that the induced epithelial-mesenchymal transition is reversible, and that the degree of reversibility depends on the MWCNT.

Long-term pulmonary exposure to multi-walled carbon nanotubes promotes breast cancer metastatic cascades

2019 ◽  
Vol 14 (7) ◽  
pp. 719-727 ◽  
Author(s):  
Xuefei Lu ◽  
Yong Zhu ◽  
Ru Bai ◽  
Zhengsheng Wu ◽  
Wenchang Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbon Nanotubes ◽  
Pulmonary Exposure ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

scholarly journals Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial–mesenchymal transition

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Chaoju Gong ◽  
Jie Shen ◽  
Zejun Fang ◽  
Lei Qiao ◽  
Ruifang Feng ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Epithelial Marker ◽  
Cancer Genome Atlas

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell–cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial–mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis.

scholarly journals Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fat-Moon Suk ◽  
Chao-Lien Liu ◽  
Ming-Hua Hsu ◽  
Yu-Ting Chuang ◽  
Jack P. Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Benzimidazole Derivative ◽  
Acquired Resistance ◽  
Xenograft Model ◽  
Side Chain ◽  
Mesenchymal Transition ◽  
New Compounds ◽  
Line Drug

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Currently, sorafenib is the standard first-line drug for patients with advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity of tumour cells to the drug, leading to acquired resistance. Therefore, developing new compounds to treat sorafenib resistance is urgently needed. Although benzimidazole and its derivatives have been reported to exert antimicrobial and antitumour effects, the anti-drug resistance potential of these molecules is still unknown. In this study, we established sorafenib-resistant (SR) cell lines and an acquired sorafenib resistance xenograft model. We showed that treatment with a benzimidazole derivative bearing a pyrrolidine side chain (compound 9a) inhibited the proliferation of SR cells by blocking the phosphorylation of AKT, p70S6 and the downstream molecule RPS6. In addition, caspase 3/PARP-dependent apoptotic signals were induced in 9a-treated cells. Regarding epithelial-mesenchymal transition (EMT) activities, 9a treatment significantly suppressed the migration of SR cells. In particular, the levels of EMT-related transcription factors (snail, slug and twist) and mesenchymal markers (vimentin and N-cadherin) were downregulated. In the acquired sorafenib resistance xenograft model, compound 9a administration decreased the growth of tumours with acquired sorafenib resistance and the expression of the HCC markers α-fetoprotein, glypican 3 and survivin. In conclusion, treatment with this compound may be a novel therapeutic strategy for patients with sorafenib resistance.

The role of miR-29 in pulmonary fibrosis

2015 ◽  
Vol 93 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Leah Cushing ◽  
Pingping Kuang ◽  
Jining Lü
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Pathological Condition ◽  
Lung Parenchyma ◽  
Interstitial Lung Diseases ◽  
Toxic Substances ◽  
Chronic Infections ◽  
Mesenchymal Transition

Pulmonary fibrosis is a pathological condition in which lungs become scarred due to the excess extracellular matrix (ECM) deposition and structural alterations in the interstitium of lung parenchyma. Many patients with interstitial lung diseases (ILDs) caused by long-term exposure to toxic substances, chronic infections, or autoimmune responses develop fibrosis. Etiologies for many ILDs are unknown, such as idiopathic pulmonary fibrosis (IPF), a devastating, relentless form of pulmonary fibrosis with a median survival of 2–3 years. Despite several decades of research, factors that initiate and sustain the fibrotic response in lungs remain unclear and there is no effective treatment to block progression of fibrosis. Here we summarize recent findings on the antifibrotic activity of miR-29, a small noncoding regulatory RNA, in the pathogenesis of fibrosis by regulating ECM production and deposition, and epithelial–mesenchymal transition (EMT). We also describe interactions of miR-29 with multiple profibrotic and inflammatory pathways. Finally, we review the antifibrotic activity of miR-29 in animal models of fibrosis and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis.

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