scholarly journals Secretomes of Primary Cancer-associated Fibroblasts Upregulate the Expression of Stemness Markers in HT-29 Human Colorectal Carcinoma Cells

2020 ◽  
Vol 12 (4) ◽  
pp. 333-339
Author(s):  
Septelia Inawati Wanandi ◽  
Dwi Retna Lestari ◽  
Noza Hilbertina ◽  
Nurjati Chairani Siregar ◽  
Sri Widia Jusman ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Stroma ◽  
Cancer Associated Fibroblasts ◽  
Trypan Blue Exclusion ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
And Control ◽  
Ht 29

BACKGROUND: Cancer-associated fibroblast (CAF) is the most abundant tumor stroma. Our previous study has demonstrated that the secretomes of CAF isolated from colorectal carcinoma (CRC) patients could induce epithelial-mesenchymal transition in the HT-29 CRC cell line. However, the role of CAF secretomes in CRC stemness is needed to be further investigated. Therefore, the present study aimed to investigate the effect of CAF secretomes from CRC patients on the expression of stemness markers in HT-29 CRC cells in comparison with the secretomes from normal fibroblasts.METHODS: Fibroblasts were isolated from tumor (CAF) and their counterpart non-tumor (NF) areas of three CRC patients undergone surgical resection. Normal preputium fibroblasts (PF) were isolated during circumcision of three healthy boys aged 8 years. All fibroblasts were grown in free-serum culture medium for 24 hours to collect 50% (v/v) conditioned medium (CM). Then, CM was supplemented to HT-29 CRC cells for 72 hours. The effects of CAF- and NF-CM on the mRNA expression of CD44, CD133, OCT4, and ALDH1A1 were analysed using qRT-PCR. Cells proliferation was measured using the trypan blue exclusion assay.RESULTS: Supplementation of CAF-CM (50% v/v) significantly increased CD44, CD133, OCT4, and ALDH1A1 mRNA expressions compared to that of NF-CM and control without supplementation but had no effect on the proliferation of HT-29 cells.CONCLUSION: CAF secretomes from CRC patients upregulate the expression of CRC stemness.KEYWORDS: cancer-associated fibroblasts, ALDH1A1, OCT4, CD44, CD133, colorectal carcinoma

scholarly journals The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1723 ◽  
Author(s):  
Jacopo Baglieri ◽  
David Brenner ◽  
Tatiana Kisseleva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Hepatic Inflammation ◽  
Therapeutic Approaches ◽  
Chronic Liver Injury ◽  
Mesenchymal Transition ◽  
Liver Fibrogenesis ◽  
Tumor Growth And Invasion

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and lacks effective therapeutic approaches. Most HCC develops in the setting of chronic liver injury, hepatic inflammation, and fibrosis. Hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs) are key players in liver fibrogenesis and hepatocarcinogenesis, respectively. CAFs, which probably derive from HSCs, activate into extracellular matrix (ECM)-producing myofibroblasts and crosstalk with cancer cells to affect tumor growth and invasion. In this review, we describe the different components which form the HCC premalignant microenvironment (PME) and the tumor microenvironment (TME), focusing on the liver fibrosis process and the biology of CAFs. We will describe the CAF-dependent mechanisms which have been suggested to promote hepatocarcinogenesis, such as the alteration of ECM, CAF-dependent production of cytokines and angiogenic factors, CAF-dependent reduction of immuno-surveillance, and CAF-dependent promotion of epithelial-mesenchymal transition (EMT). New knowledge of the fibrosis process and the role of CAFs in HCC may pave the way for new therapeutic strategies for liver cancer.

scholarly journals Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yingyan Wang ◽  
Wen Lan ◽  
Mingxin Xu ◽  
Jing Song ◽  
Jun Mao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
Stromal Cell Derived Factor ◽  
Targeted Approach

AbstractCancer-associated fibroblasts (CAFs) contribute to tumour epithelial-mesenchymal transition (EMT) via interaction with cancer cells. However, the molecular mechanisms underlying tumour-promoting EMT of CAFs in lung adenocarcinoma (ADC) remain unclear. Here, we observed that CAFs isolated from lung ADC promoted EMT via production of stromal cell-derived factor-1 (SDF-1) in conditioned medium (CM). CAF-derived SDF-1 enhanced invasiveness and EMT by upregulating CXCR4, β-catenin, and PPARδ, while downregulating these proteins reversed the effect. Furthermore, RNAi-mediated CXCR4 knockdown suppressed β-catenin and PPARδ expression, while β-catenin inhibition effectively downregulated PPARδ without affecting CXCR4; however, treatment with a PPARδ inhibitor did not inhibit CXCR4 or β-catenin expression. Additionally, pairwise analysis revealed that high expression of CXCR4, β-catenin, and PPARδ correlated positively with 75 human lung adenocarcinoma tissues, which was predictive of poor prognosis. Thus, targeting the CAF-derived, SDF-1-mediated CXCR4 β-catenin/ PPARδ cascade may serve as an effective targeted approach for lung cancer treatment.

Targeting Galectin-1 by Aflibercept Strongly Enhances Its Antitumor Effect in Neuroendocrine Carcinomas

2020 ◽  
Vol 111 (1-2) ◽  
pp. 146-157 ◽  
Author(s):  
María Rodríguez-Remírez ◽  
Laura del Puerto-Nevado ◽  
María Jesús Fernández-Aceñero ◽  
Marlid Cruz-Ramos ◽  
Laura García-García ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Pancreatic Tumors ◽  
Matrix Remodeling ◽  
Antiangiogenic Effect ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
Promising Target ◽  
Neuroendocrine Carcinomas

<b><i>Background:</i></b> Galectin-1 (Gal-1) plays major roles in cancer by modulating different processes leading to tumor development and progression. In the last years, it has been suggested as a promising target for anticancer therapy. Recently, aflibercept has shown high affinity for Gal-1. Here, we investigated how aflibercept could exert its antitumor activity via Gal-1-driven pathways in neuroendocrine carcinomas (NECs). <b><i>Methods and Results:</i></b> NEC tumor xenografts were used to assess the effect of aflibercept on Gal-1 functions. Aflibercept induced a significant reduction of Gal-1 at epithelial, stromal, and extracellular localizations in lung NEC, whereas this was not observed in colon NECs, which displayed low expression of Gal-1. Additionally, aflibercept significantly reduced p-VEGFR2 protein, extracellular matrix remodeling, epithelial-mesenchymal transition, and activation of cancer-associated fibroblast hampering cell invasion in lung NEC but not in colon NEC. Gal-1 screening in human NECs confirmed that pulmonary and pancreatic tumors displayed higher levels of Gal-1 than colon NECs, becoming good candidates to benefit from aflibercept treatment. <b><i>Conclusions:</i></b> The lack of validated predictive markers of aflibercept is a weakness for guaranteeing the best treatment management with this drug. This work provides new mechanistic insight of aflibercept depending on Gal-1. Thus, in tumors overexpressing Gal-1, aflibercept has not only an antiangiogenic effect but also prevents Gal-1-mediated tumor-stroma cross talk. The stronger aflibercept effect in tumors with high levels of Gal-1 points out this protein as a molecular marker to predict the efficacy of this agent not only for NECs but also for other tumors with high levels of this protein.

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

scholarly journals Correction to: The role of epithelial–mesenchymal transition (EMT)-associated genes during gonadogenesis of albino rat

2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Lina A. Aeshra ◽  
Maiada Moustafa ◽  
Mohammed I. Y. Elmallah ◽  
Said Abdelrahman Salih ◽  
Ibrahim Y. Abdel Kader
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Albino Rat ◽  
Mesenchymal Transition
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