scholarly journals Inflammation during Lung Cancer Progression and Ethyl Pyruvate Treatment Observed by Pulmonary Functional Hyperpolarized 129Xe MRI in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Atsuomi Kimura ◽  
Seiya Utsumi ◽  
Akihiro Shimokawa ◽  
Renya Nishimori ◽  
Neil J. Stewart ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gas Exchange ◽  
Cancer Progression ◽  
Ethyl Pyruvate ◽  
Late Phase ◽  
Precancerous Lesion ◽  
Lung Ventilation ◽  
Negative Control ◽  
Functional Changes ◽  
Hyperpolarized 129Xe

This study aimed to assess the suitability of hyperpolarized 129Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice (N = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane (N = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline ( P < 0.01 ). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy.

scholarly journals Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes

QJM ◽  
2019 ◽  
Vol 112 (8) ◽  
pp. 581-590 ◽  
Author(s):  
J You ◽  
M Li ◽  
L M Cao ◽  
Q H Gu ◽  
P B Deng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Negative Control ◽  
Lung Cancer Cells ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Background Epithelial-mesenchymal transition (EMT) is an essential component of metastasis. Our previous study demonstrated that cancer-associated fibroblasts (CAFs) induce EMT in lung cancer cells. In recent years, many studies have demonstrated that CAFs induce metastasis and drug resistance in cancer cells via exosomes. Aim We sought to discover the mechanism underlying how CAFs induce EMT in lung cancer cells, unveiling the role of exosomes in lung cancer progression. Design We cultured lung cancer cell (i) with control medium, normal fibroblasts (NFs) or CAFs; (ii) with SNAI1-transfected or NC (negative control)-transfected CAFs; (iii) with exosomes extracted from NF- or CAF-conditioned medium; (iv) with exosomes released by SNAI1 or NC-transfected CAFs; (v) with CAF-conditioned medium or exosome-depleted CAF-conditioned medium. Methods qRT-PCR was conducted to examine the expression of CDH1 (gene of E-cadherin) and VIM (gene of Vimentin), western blotting was conducted to examine E-cadherin and vimentin levels in lung cancer cells. Results Exosomes released by CAFs-promoted EMT in lung cancer cells. Interestingly, SNAI1 levels in exosomes secreted from CAFs were correlated with SNAI1 expression in CAFs. Furthermore, the level of SNAI1 in exosomes was crucial for inducing EMT in lung cancer cells. Finally, treatment of CAFs with GW4869, an inhibitor of exosome release, noticeably inhibited their EMT-inducing effect on recipient epithelial cells. Conclusions The molecular mechanism underlying how CAFs induce EMT in cancer cells may be that CAFs deliver SNAI1 to recipient cancer cells via exosomes.

The value of sperm-associated antigen 9 in lung cancer progression

2018 ◽  
Author(s):  
Merih Tepeoglu ◽  
Ebru Sebnem Ayva ◽  
B. Handan Ozdemir
Keyword(s):  
Lung Cancer ◽  
Cancer Progression

scholarly journals αvβ3 Integrin induces partial EMT independent of TGF-β signaling

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshinobu Kariya ◽  
Midori Oyama ◽  
Takato Suzuki ◽  
Yukiko Kariya
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Αvβ3 Integrin ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Intermediate States ◽  
Tgf Β1

AbstractEpithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.

scholarly journals LINC01089 functions as a ceRNA for miR-152-3p to inhibit non‐small lung cancer progression through regulating PTEN

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huixian Zhang ◽  
Hao Zhang ◽  
Xingya Li ◽  
Siyuan Huang ◽  
Qianqian Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Expression Level ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Protein Coding ◽  
Tensin Homolog ◽  
Pten Mrna

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

Sign in / Sign up

Export Citation Format

Share Document