scholarly journals Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4122
Author(s):  
Jing Song ◽  
Peiyan Yang ◽  
Xiuwen Li ◽  
Xinyi Zhu ◽  
Mengxin Liu ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Magnetic Beads ◽  
Epithelial Mesenchymal Transition ◽  
Macrophage Polarization ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Mesenchymal Transition ◽  
Esophageal Cancer Cells

The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs.

scholarly journals Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lin-pei Wang ◽  
Jing Lin ◽  
Xiao-qiu Ma ◽  
Dong-yao Xu ◽  
Chun-feng Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Macrophage Polarization ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Mesenchymal Transition ◽  
M2 Macrophage Polarization ◽  
Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) cells-secreted exosomes (exo) could stimulate M2 macrophage polarization and promote HCC progression, but the related mechanism of long non-coding RNA distal-less homeobox 6 antisense 1 (DLX6-AS1) with HCC-exo-mediated M2 macrophage polarization is largely ambiguous. Thereafter, this research was started to unearth the role of DLX6-AS1 in HCC-exo in HCC through M2 macrophage polarization and microRNA (miR)-15a-5p/C-X-C motif chemokine ligand 17 (CXCL17) axis. Methods DLX6-AS1, miR-15a-5p and CXCL17 expression in HCC tissues and cells were tested. Exosomes were isolated from HCC cells with overexpressed DLX6-AS1 and co-cultured with M2 macrophages. MiR-15a-5p/CXCL17 down-regulation assays were performed in macrophages. The treated M2 macrophages were co-cultured with HCC cells, after which cell migration, invasion and epithelial mesenchymal transition were examined. The targeting relationships between DLX6-AS1 and miR-15a-5p, and between miR-15a-5p and CXCL17 were explored. In vivo experiment was conducted to detect the effect of exosomal DLX6-AS1-induced M2 macrophage polarization on HCC metastasis. Results Promoted DLX6-AS1 and CXCL17 and reduced miR-15a-5p exhibited in HCC. HCC-exo induced M2 macrophage polarization to accelerate migration, invasion and epithelial mesenchymal transition in HCC, which was further enhanced by up-regulated DLX6-AS1 but impaired by silenced DLX6-AS1. Inhibition of miR-15a-5p promoted M2 macrophage polarization to stimulate the invasion and metastasis of HCC while that of CXCL17 had the opposite effects. DLX6-AS1 mediated miR-15a-5p to target CXCL17. DLX6-AS1 from HCC-exo promoted metastasis in the lung by inducing M2 macrophage polarization in vivo. Conclusion DLX6-AS1 from HCC-exo regulates CXCL17 by competitively binding to miR-15a-5p to induce M2 macrophage polarization, thus promoting HCC migration, invasion and EMT.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

scholarly journals [ARTICLE WITHDRAWN] MicroRNA-539 Inhibits the Epithelial‐Mesenchymal Transition of Esophageal Cancer Cells by Twist-Related Protein 1-Mediated Modulation of Melanoma-Associated Antigen A4

2018 ◽  
Vol 26 (4) ◽  
pp. 529-536 ◽  
Author(s):  
Zhili Cao ◽  
Xiang Zheng ◽  
Lei Cao ◽  
Naixin Liang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
The United States ◽  
Research Data ◽  
Original Study ◽  
Related Protein ◽  
Mesenchymal Transition ◽  
Scientific Nature ◽  
Esophageal Cancer Cells

This article has been withdrawn at the request of the author in December 2020. STATEMENT FOR WITHDRAWAL OF MANUSCRIPT FROM ONCOLOGY RESEARCH Dear Editors, I am Dr. Naixin Liang. For some scientific reasons, my team and I are very sorry to apply to withdraw the manuscript "MicroRNA-539 Inhibits the Epithelial-Mesenchymal Transition of Esophageal Cancer Cells By Twist-Related Protein 1-Mediated Modulation of Melanoma Associated Antigen A4 (MAGEA4)". DOI: 10.3727/096504017 x14972679378357 Because of COVID-19, the lab we worked together was no longer functioning and closed. When reviewing the data of the paper completed in cooperation with the original laboratory, we found that some of the data in the above article were not scientific enough, some Western Blot images were not clear enough (as in FIG 1, the band of α-SMA was blurt and do not seem darker than vimentin but lighter than E-adherin), and some of the research data contained excessive standard errors (as in FIG 2B, standard error of vimentin and α-SMA of miR-539 mimic +Pb-TWIST1(IV) were too large , so the average of the expression may be not accurate), which may lead to the researchers' wrong interpretation of the data and misjudgment of its scientific nature. For the sake of rigor, we took the initiative to contact the experimental operator of the original study. Unfortunately, the person who completed the primary operation of the original study has left China to study in the United States. Due to COVID-19 and other reasons, we could not contact this experimenter to confirm the original research data, so we cannot repeat and verify the data for the time being. As the corresponding author, after found the problem, I contacted Dr. Zhili Cao and Xiang Zheng, and the other author, Dr. Lei Cao at the first time. I told them all the thing we found above. After careful discussion, all the author agreed that, based on the need of scientific, rigor, we are deeply sorry to apply to the editorial office for withdraw the paper. My team and I have noticed that your journal has been developing very well in recent years, and its impact factors have been rising all the way. Congratulations to your team! We are very sorry that there may be errors in our interpretation of the data due to our imprecise interpretation, thus affecting the scientific nature of the conclusion of the article. My team and I have complied with the AGREEMENT FOR WITHDRAWAL OF MANUSCRIPT, and have completed the payment of the fee on December 4, 2020, 300$. Please see the attachment for related procedures. We hope your journal would approve our application for retraction of this article. Sincerely Yours, Naixin Liang 2020.12.4

scholarly journals Macrophages-aPKCɩ-CCL5 Feedback Loop Modulates the Progression and Chemoresistance in Cholangiocarcinoma

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Tao Yang ◽  
Zhengdong Deng ◽  
Lei Xu ◽  
Xiangyu Li ◽  
Tan Yang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Cationic Liposome ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Blood Monocytes ◽  
Antitumor Effects ◽  
Mesenchymal Transition

Abstract Background Recent data indicated that macrophages may mutually interact with cancer cells to promote tumor progression and chemoresistance, but the interaction in cholangiocarcinoma (CCA) is obscure. Methods 10x Genomics single-cell sequencing technology was used to identified the role of macrophages in CCA. Then, we measured the expression and prognostic role of macrophage markers and aPKCɩ in 70 human CCA tissues. Moreover, we constructed monocyte-derived macrophages (MDMs) generated from peripheral blood monocytes (PBMCs) and polarized them into M1/M2 macrophages. A co-culture assay of the human CCA cell lines (TFK-1, EGI-1) and differentiated PBMCs-macrophages was established, and functional studies in vitro and in vivo was performed to explore the interaction between cancer cells and M2 macrophages. Furthermore, we established the cationic liposome-mediated co-delivery of gemcitabine and aPKCɩ-siRNA and detect the antitumor effects in CCA. Results M2 macrophage showed tumor-promoting properties in CCA. High levels of aPKCɩ expression and M2 macrophage infiltration were associated with metastasis and poor prognosis in CCA patients. Moreover, CCA patients with low M2 macrophages infiltration or low aPKCɩ expression benefited from postoperative gemcitabine-based chemotherapy. Further studies showed that M2 macrophages-derived TGFβ1 induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance in CCA cells through aPKCɩ-mediated NF-κB signaling pathway. Reciprocally, CCL5 was secreted more by CCA cells undergoing aPKCɩ-induced EMT and consequently modulated macrophage recruitment and polarization. Furthermore, the cationic liposome-mediated co-delivery of GEM and aPKCɩ-siRNA significantly inhibited macrophages infiltration and CCA progression. Conclusion our study demonstrates the role of Macrophages-aPKCɩ-CCL5 Feedback Loop in CCA, and proposes a novel therapeutic strategy of aPKCɩ-siRNA and GEM co-delivered by liposomes for CCA.

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