scholarly journals Embryonic Trophectoderm Secretomics Reveals Chemotactic Migration and Intercellular Communication of Endometrial and Circulating MSCs in Embryonic Implantation

2021 ◽  
Vol 22 (11) ◽  
pp. 5638
Author(s):  
Alexandra Calle ◽  
Víctor Toribio ◽  
María Yáñez-Mó ◽  
Miguel Ángel Ramírez
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Soluble Fraction ◽  
Primary Cultures ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Angiogenic Proteins ◽  
Uterine Fluid ◽  
Related Proteins ◽  
Implantation Period

Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period.

scholarly journals Embryonic trophectoderm secretomics reveals chemotactic migration and intercellular communication of endometrial and circulating MSCs in embryonic implantation

2021 ◽  
Author(s):  
Alexandra Calle ◽  
Víctor Toribio-Serrano ◽  
María Yáñez-Mó ◽  
Miguel Ángel Ramírez
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Soluble Fraction ◽  
Primary Cultures ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Angiogenic Proteins ◽  
Uterine Fluid ◽  
Related Proteins ◽  
Implantation Period

Abstract Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial-mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures and 8 endometrial MSC (eMSC) and 5 peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: i) their epithelial-mesenchymal phenotype; ii) as a result of the uptake of eMSC- or pbMSC-EVs previously stimulated or not with embryonic signals (IFN-τ), and iii) because of stimulation with endometrial cytokines present in the uterine fluid in the peri-implantation period.

scholarly journals Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype

2021 ◽  
Author(s):  
Sarthak Sahoo ◽  
Sonali Priyadarshini Nayak ◽  
Kishore Hari ◽  
Susmita Mandal ◽  
Akash Kishore ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Causal Link ◽  
M Cells ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Secondary Tumour

Cancer metastasis remains a primary cause of cancer related mortality. Recent in vitro and in vivo data has indicated the high metastatic fitness of hybrid epithelial/mesenchymal (E/M) states, i.e. their enhanced abilities to initiate tumours at secondary tumour site. Mechanistic details about how such hybrid E/M cells survive the metastatic cascade remain unclear. Here, we investigate immune-evasive strategies of hybrid E/M states, an issue that to date has been largely unexplored. We construct a minimalistic regulatory network that captures known associations between regulators of EMT (the epithelial mesenchymal transition) and levels of PD-L1, an established suppressor of immune response, and simulated the network's emergent dynamics. Our model recapitulates observations that cells undergoing EMT have increased PD-L1 levels, while reverting EMT can decrease these levels, indicative of a causal link between EMT drivers and PD-L1. Further, we show that hybrid E/M cells can have high levels of PD-L1, similar to those seen in cells with a full EMT phenotype, thus obviating the need for cancer cells to undergo a full EMT to evade the immune system. Finally, we identify various signalling pathways and cellular processes that can independently or in concert affect PD-L1 levels and EMT status. For instance, hybrid E/M cells can gain both immune-evasion and stemness through largely independent paths. Our results underscore another underlying reason for the high metastatic ability of hybrid E/M cells.

scholarly journals Down-Regulated MAC30 Suppresses Lung Cancer Invasion and EMT by Inhibiting Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
jingzhu zhou ◽  
xiuhai ji ◽  
ruhua chen ◽  
yan fen ◽  
Hui ding
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Cancer Invasion ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Related Proteins ◽  
Proliferation And Invasion ◽  
Worse Prognosis

Abstract Backgrounds：Over-expressed meningioma-associated protein (MAC30) was proved to be a biomarker for worse prognosis in non–small cell lung cancer (NSCLC). However, the regulated mechanism of MAC30 in epithelial–mesenchymal transition (EMT) and lung cancer invasion is unknown. Methods：Transformed growth factor (TGF-β) was used to induce EMT in A549 cells in vitro. MAC30 siRNA was transfected into cells to silence the gene expression. Real-Time PCR was prepared to assess the levels of MAC30 mRNA. Methyl thiazolyl tetrazolium (MTT) and Transwell invasion assays were performed to study the proliferation and invasion of A549 cells. Expression of MAC30, EMT-related proteins, Wnt/β-catenin signal and its downstream factors were explored by ELISA. Results: We found enhanced MAC30 expression in A549 cells. MAC30 Knockdown inhibited TGF-β-induced lung cell proliferation and invasion. Furthermore, elevated levels of mesenchymal markers (N-cadherin, vimentin) and decreased levels of epithelial markers E-cadherin in A549 cells with TGF-β incubation were reversed by MAC30 siRNA. Finally, MAC30 knockdown significantly suppressed TGF-β-upregulated protein levels of Wnt/ β-catenin signaling and its downstream genes (surviving, c-myc and cyclin D1). Conclusions: We firstly confirm that MAC30 knockdown limits lung cancer growth and EMT through inhibiting the activation of Wnt/β-catenin pathway.

Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process

2018 ◽  
Vol 399 (6) ◽  
pp. 593-602 ◽  
Author(s):  
Hongchao He ◽  
Jun Dai ◽  
Xiaoqun Yang ◽  
Xiaojing Wang ◽  
Fukang Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Tumor Xenograft ◽  
Mesenchymal Transition ◽  
Related Proteins ◽  
The Impact

AbstractThis study aimed to explore the effect ofMED27on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC). The functional mechanism ofMED27on ACC processes was also explored. The expression ofMED27was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was utilized to knockdown the expression ofMED27. CCK8 assays were performed to evaluate SW-13 cell proliferation. Transwell assays were performed to assess the invasion ability, and wound healing assays were utilized to detect migration. A tumor xenograft mouse model was established to investigate the impact of silencingMED27on tumor growth and metastasis.MED27was highly expressed in ACC tissues and cells. Down-regulation ofMED27induced ACC cell apoptosis, and significantly attenuated ACC cell proliferation, invasion and metastasisin vivoandin vitro.MED27knockdown regulated the expression of EMT-related proteins and Wnt/β-catenin signaling pathway-related proteins. Our study investigated the function and mechanism ofMED27and validated thatMED27plays a negative role in ACC occurrence and progression and could be utilized as a new therapeutic target in ACC prevention and treatment.

scholarly journals miR-193a-3p Mediates Placenta Accreta Spectrum Development by Targeting EFNB2 via Epithelial-Mesenchymal Transition Pathway Under Decidua Defect Conditions

2021 ◽  
Vol 7 ◽  
Author(s):  
Na Li ◽  
Rui Hou ◽  
Tian Yang ◽  
Caixia Liu ◽  
Jun Wei
Keyword(s):  
Conditioned Medium ◽  
Epithelial Mesenchymal Transition ◽  
Placenta Accreta ◽  
Migration And Invasion ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Placenta Accreta Spectrum ◽  
Related Proteins ◽  
Cells Cultured

Objective: To clarify the role of microRNA-193a-3p (miR-193a-3p) in the pathogenesis of placenta accreta spectrum.Methods: The placental tissue expression levels of miR-193a-3p and Ephrin-B2 (EFNB2) were compared between a placenta accreta spectrum group and a control group. Transwell migration and invasion assays were used to verify the effect of miR-193a-3p and EFNB2 on HTR-8/SVneo cells cultured in human endometrial stromal cell (hESC)-conditioned medium. Epithelial-mesenchymal transition (EMT)-related proteins were examined by western blotting to establish whether the EMT pathway was altered in placenta accreta spectrum. To determine whether EFNB2 is a target gene of miR-193a-3p, luciferase activity assays were performed.Results: miR-193a-3p was upregulated but EFNB2 downregulated in the placenta accreta spectrum group and EFNB2 was a direct target of miR-193a-3p. Overexpression or inhibition of miR-193a-3p revealed that miR-193a-3p promoted the migration and invasion of HTR-8/SVneo cells cultured in hESC-conditioned medium. Furthermore, EMT was induced, as shown by increased N-cadherin, vimentin, MMP2, and MMP9 and decreased E-cadherin in the placenta accreta spectrum group and in HTR-8/SVneo cells transfected with miR-193a-3p mimics or si-EFNB2. The negative effect of miR-193a-3p inhibitor was reversed by co-transfection with si-EFNB2 in function studies and in analyses of EMT-related proteins in vitro.Conclusion: miR-193a-3p which upregulated in placenta accreta spectrum group increases HTR-8/SVneo cell migration and invasion by targeting EFNB2 via the EMT pathway under decidua defect conditions to lead to placenta accreta spectrum.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

scholarly journals MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

2021 ◽  
Vol 20 ◽  
pp. 153303382198981
Author(s):  
Xin-bo Sun ◽  
Yong-wei Chen ◽  
Qi-sheng Yao ◽  
Xu-hua Chen ◽  
Min He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Proliferation And Apoptosis ◽  
High Incidence ◽  
Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

scholarly journals Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 965
Author(s):  
Grazia Maugeri ◽  
Agata Grazia D’Amico ◽  
Salvatore Saccone ◽  
Concetta Federico ◽  
Daniela Maria Rasà ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Hypoxic Area ◽  
Vitro Model ◽  
Human Gbm ◽  
Endothelial Growth Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

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