Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-β1 induced epithelial-mesenchymal transition

Zhou, Haisen; Su, Xiao-Fang; Fu, Xingli; Wang, Guozhong; Luo, Kun; Zheng, Fang; Yu, Feng; Liu, Hong; Hu, Hongjuan; Chen, Liusheng; Cai, Bing; Tian, Zhiqiang

doi:10.18632/oncotarget.9319

Cited by 19 publications

(11 citation statements)

References 38 publications

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“…The occurrence of EMT is closely associated with the tumor microenvironment and inflammation ( 14 ). Mesenchymal stem cells (MSCs), which have multiple differentiation potential and specific chemotaxis toward tumor tissue, can be used as carriers for targeted delivery of suicide genes, growth factor inhibitors, and oncolytic viruses to tumor tissues ( 15 ). However, MSCs can also promote tumor growth by immune inhibition, promoting angiogenesis, and by other mechanisms ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition

2017

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The characteristics of cancer cells, such as invasiveness, are affected by the tumor microenvironment. Studies have shown that interleukin (IL)-6 and tumor necrosis factor (TNF)-α regulate the proliferation of lung cancer. However, few studies have focused on the effects of IL-6 and TNF-α on metastasis of lung cancer. The present study was designed to investigate whether IL-6 and TNF-α can promote metastasis of non-small cell lung cancer (NSCLC). Sixty-five tumor and matched adjacent tissue samples from patients with NSCLC and corresponding serum samples were collected. Thirty serum samples from healthy subjects were selected as controls. Real-time PCR and western blot analysis were used to measure IL-6, TNF-α, vimentin, E-cadherin, and N-cadherin expression in tissue samples; ELISA was used to measure IL-6 and TNF-α expression in serum samples. The correlation of serum levels of IL-6 and TNF-α with the clinical stage was analyzed; the correlation of IL-6 and TNF-α levels in serum with these tissues was analyzed; the correlation of serum levels of IL-6 and TNF-α with lymph node metastasis and distant metastasis was analyzed. Expression of IL-6 and TNF-α were significantly increased compared with controls in both serum and tissue; IL-6 and TNF-α levels were positively correlated with lymph node metastasis and distant metastasis; IL-6 and TNF-α levels were negatively correlated with E-cadherin level and were positively correlated with N-cadherin and vimentin levels. In conclusion, IL-6 and TNF-α can induce epithelial-mesenchymal transition, and subsequently promote metastasis of lung cancer. Anti-inflammation should be considered for the treatment of lung cancer.

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Section: Discussionmentioning

confidence: 99%

IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition

2017

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“… 77 , 78 Several studies have shown that MSCs can either promote or inhibit tumor progression in different tumor models. 79 , 80 , 81 , 82 However, the mechanisms by which MSCs control tumor cells remain unclear.…”

Section: Therapeutic Properties Of Msc-derived Exosomes On Liver Disementioning

confidence: 99%

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

et al. 2017

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The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs. They are smaller and less complex than their parent cells and, thus, easier to produce and store, they are devoid of viable cells, and they present no risk of tumor formation. Moreover, they are less immunogenic than their parent cells because of their lower content in membrane-bound proteins. This paper reviews the biogenesis of MSC exosomes and their physiological functions, and highlights the specific biochemical potential of MSC-derived exosomes in restoring tissue homeostasis. In addition, we summarize the recent advances in the role of exosomes in MSC therapy for various liver diseases, including liver fibrosis, acute liver injury and hepatocellular carcinoma. This paper also discusses the potential challenges and strategies in the use of exosome-based therapies for liver disease in the future.

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“…This epigenetic mechanism, represented by the mir-199-a/LCOR/interferon axis, mediates the evasion from the autocrine and immune microenvironment-mediated suppressive cross-talk, and is conserved in normal SCs and CSCs. These finding may be both mechanistically and pharmacologically strategic, taking also into account that the inflammatory microenvironment can promote EMT-linked cell invasion [ 77 , 78 , 79 ].…”

Section: Emt-induced Spheroids As An In Vitro Model Of Stem Cell Nmentioning

confidence: 99%

EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

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Rosa

et al. 2017

Cancers

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The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target.

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Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-β1 induced epithelial-mesenchymal transition

Cited by 19 publications

References 38 publications

IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition

IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

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