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Epigenetic reprogramming of epithelial mesenchymal transition in triple negative breast cancer cells with DNA methyltransferase and histone deacetylase inhibitors

Epigenetic reprogramming of epithelial mesenchymal transition in triple negative breast cancer cells with DNA methyltransferase and histone deacetylase inhibitors

another (cell adhesion). EpCAM has been considered as an oncogenic signal transducer, the cleaved EpCAM helps relay signals from outside of cells to nucleus, resulting to cross-talk to other signaling including WNT pathway [49]. In our study, we observed a decrease of TCF4 by DNMTi and HDACi in mesenchymal-like cell lines. It is of importance that the combined treatment of SGI with MS275 synergistically increases full-length EpCAM, inhibits TCF4, and upregulates E-cadherin. Based on these findings, we postulate that the cleavage of N-terminal EGF-like domain of EpCAM may cause the internalization of the cleaved EpCAM, which cross-talks with WNT signaling and other pathways, contributing to EMT process. The combined treatment of SGI with MS275 synergistically inhibits the cleavage of EpCAM, thus suppresses WNT signaling and reverses EMT. Giving the fact that WNT/beta-catenin signaling is related to TNBC tumorigenesis and metastasis [50, 51], and there are no drugs targeting WNT pathways currently approved for the treatment of TNBC, our re- sults strongly suggest combined treatment of SGI with MS275 could be a strategy targeting EMT through WNT pathway in TNBC.

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Hepatitis C virus NS4B protein induces epithelial mesenchymal transition by upregulation of Snail

Hepatitis C virus NS4B protein induces epithelial mesenchymal transition by upregulation of Snail

plasmids into HepG2 cells, and then we examined the hallmarks of EMT at 48 h. It was found that cells trans- fected with pNS4B plasmids had lower expression of E-cadherin and higher expression of N-cadherin than the cells transfected with empty vector, as similar to the EMT phenotype in HCVcc infected cells, suggesting that HepG2 cells were in EMT procession (Fig. 2a). Further- more, we transfected empty vector, pNS4B plasmids (1, 3, 5 μg) in HepG2 cells to investigate whether the EMT process was related to NS4B levels, at 48 h post transfec- tion, we found that the expression of E-cadherin decreased gradually and N-cadherin upregulated, along with the levels of pNS4B plasmids increased. These results indicated that HCV NS4B was the reason for HepG2 cell EMT (Fig. 2b). In addition, the qRT-PCR re- sults showed that E-cadherin mRNA levels were decreased and the expression levels of N-cadherin increased after pNS4B plasmids transfection (Fig. 2c). Immunofluorescence analysis also confirmed the decreased expression of epithelial marker E-cadherin and increased expression of mesenchymal marker N-cadherin (Fig. 2d). These results demonstrated that NS4B contributed to promoting HepG2 cells EMT.

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Tetraspanin in oncogenic epithelial mesenchymal transition

Tetraspanin in oncogenic epithelial mesenchymal transition

There  are  both  similarities  and  differ- ences between the TM4SF5-induced EMT  of SNU449 cells reported in this issue by  Lee et al. (15) and the EMT models of mam- mary gland or hepatic origin (Table 1). In  all EMT models, the expression of epithelial  cell markers is downregulated, while that of  mesenchymal cell markers is upregulated.  In all such models, one of the distinct fea- tures of EMT is the formation of actin stress  fibers (17–19), which are thought to con- tribute to increased cell motility. However,  stress fiber formation was not observed by  Lee et al. in their SNU449 cells in the current  study. Also, in other EMT models (19–22),   E-cadherin  downregulation  is  mediated  by  the  transcriptional  repressor  Snail1,  but  in  the  current  study  (15),  TM4SF5- induced EMT of SNU449 cells appeared  to be independent of Snail1. Moreover, in  NMuMG cells, RhoA was found to function  as an upstream effector of Akt activation in  response to TGF-b, the inducer of EMT in  this cell system (23), which is in contrast to  the effect of Akt as the upstream effector to  inhibit RhoA as reported here (15). The cur- rent study by Lee et al. therefore highlights  a previously unidentified mechanism for  inducing EMT with relevance for hepatocel- lular carcinoma. Furthermore, it describes  Table 1

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Epithelial mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy?

Epithelial mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy?

Epithelial-mesenchymal transition (EMT) has become widely accepted as a mechanism by which injured renal tubular cells transform into mesenchymal cells that contribute to the development of fibrosis in chronic renal failure. However, an increasing number of studies raise doubts about the existence of this process in vivo. Herein, we review and summarize both sides of this debate, but it is our view that unequivocal evidence supporting EMT as an in vivo process in kidney fibrosis is lacking.

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Biomarkers for epithelial mesenchymal transitions

Biomarkers for epithelial mesenchymal transitions

Somatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon — namely, the transition of epithelial and endothelial cells to a motile phenotype.

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The basics of epithelial mesenchymal transition

The basics of epithelial mesenchymal transition

Inflammatory injury  to  the  mouse  kidney  can  result  in  the  recruitment of a diverse array of cells that can trigger an EMT  through their release of growth factors, such as TGF-β, PDGF,  EGF,  and  FGF-2  (57).  Most  prominent  among  these  cells  are macrophages and activated resident fibroblasts that accumulate  at the site of injury and release these growth factors. In addition,  these cells release chemokines and MMPs, notably MMP-2, MMP-3,   and MMP-9. Epithelial cells come under the influence of these sig- naling molecules and, acting together with the inflammatory cells,  induce basement membrane damage and focal degradation of type  IV collagen and laminin (57). Delaminated epithelial cells may then  migrate toward the interstitial area (the space between epithelial  layers) under the influence of gradients of growth factors and other  chemoattractants (57). This initial recruitment of epithelial cells  into an EMT can be inhibited by blocking the expression of MMP-9  through the disruption of tissue plasminogen activator (tPA) (58).  Other studies have also demonstrated that HGF can decrease levels  of TGF-β, restore TGF-β–mediated loss of E-cadherin, and poten- tially decrease amounts of active MMP-9 (59). β1 integrin and inte- grin-linked kinase (ILK) are also identified as important mediators  of the TGF-β–induced EMT associated with tubular epithelial cells  Figure 3

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Epithelial mesenchymal transitions and hepatocarcinogenesis

Epithelial mesenchymal transitions and hepatocarcinogenesis

Evidence demonstrating that EMT cor- relates  with  aggressive  biology  in  HCC  suggests that EMT conveys certain survival  advantages to tumor cells. These include  escape from apoptotic stimuli that are prev- alent within the primary tumor (TGF-β,   hypoxia)  and  improved  access  to  nutri- ents  and/or  growth  factors  (by  migrat- ing to sites remote from the competing  forces that are operative in the primary  tumor). Cells that have undergone EMT  also acquire the ability to generate factors  that stimulate production of vasculature  and  stroma.  This  property  sustains  the  outgrowth of new epithelial tumor nod- ules within or near the primary tumor and  after the subpopulations of the metastatic  (mesenchymal-appearing)  tumor  cells  have arrived in distant sites and undergone  mesenchymal-epithelial transition (MET)  to reacquire their epithelial phenotype (7).  It is therefore tempting to speculate that  situations that promote hepatocarcinogen- esis stimulate EMT and that liver cells that  have  acquired  pro-EMT  modifications,  such as CDH1L amplifications, might have  a growth advantage in such environments. Cirrhosis, EMT, and HCC

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Clinical significance of epithelial-mesenchymal transition

Clinical significance of epithelial-mesenchymal transition

However, as mentioned above, some authors also reported reexpression of epithelial markers, such as E-cadherin, along with loss of EMT-associated tran- scription factors in established metastases [41]. This apparent reversal of EMT, often referred to as mesenchymal- epithelial transition (MET), has been described for metastases of colorectal carcinoma, non-small cell lung cancer and transitional cell carcinoma [92-94]. There is an ongoing debate regarding the extent to which these findings reflect a basic mechanism in the establishment of metastases or if they are restricted to certain tumor entities or reflect distinct circumjacent conditions [4,41]. There are also critical voices that doubt the role of EMT in invasion at all, since in most histopathologic speci- mens, many tumors invade and metastasize by cohesive and multicellular rather than single-cell migration, and histopathologists rarely see abundant mesenchymal-like tumor cells in routine surgical specimens [4,95,96]. This apparent contradiction might in part be explained by re- garding EMT as a transient state of a small proportion of migrating tumor cells, with only single tumor cells or small clusters of cells obtaining the ideal dynamic configuration for different stages of invasion and me- tastasis; this reasonable compromise has been referred to as “spatial and temporal heterogeneity of EMT” by Voulgari et al. (Figure 1) [97,98].

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Epithelial to mesenchymal transition and breast cancer

Epithelial to mesenchymal transition and breast cancer

This review summarizes evidence for the growing implication of EMT in the progression of breast carcinoma, both in murine models and in humans. However, there is an urgent need for new surrogate markers to define different stages during the transition from the epithelial to mesenchymal phenotype, and the reverse transition. These markers may differ from those expressed by normal-like epithelial cells undergoing EMT. A relevant example is the well described presence of micrometastatic carcinoma cells in the blood and bone marrow that retain cytokeratin expression, and the implication of ‘hybrid’ cells in several systems. However, capturing the mesenchymal phenotype in primary tumors and metastases may prove to be a difficult task, due to the slow growth kinetics of tumors, resulting in an extended period before a mesenchymal to epithelial transition mechanism occurs. The unique topology of tumor growth in the colon has permitted the observation of rare pioneer isolated carcinomas and their likelihood to reconstitute epithelial-like glandular structures. Preliminary evidence indicates that such cells may exist in primary breast cancer, although their detection would require simultaneous labeling using three antibodies to visualize carcinoma cells in contact with endothelial cells and macrophages.

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Stability of the hybrid epithelial/mesenchymal phenotype

Stability of the hybrid epithelial/mesenchymal phenotype

While transitioning between the E and M phenotypes, cells can adopt a hybrid epithelial/ mesenchymal (E/M) or a partial EMT phenotype. Cells in this phenotype have a mix of epithelial (e.g. cell-cell adhesion) and mesenchymal (e.g. migration) traits that enable them to move collectively during mammary gland formation, trachea development, and wound healing [3, 4]. Such collective migration obviates the need for all cells to identify and respond to an external signal, and allows maximum cellular plasticity [3]. Furthermore, during metastasis, collective migration as CTC clusters has observed in the patients with lung, prostate, and breast cancer [5, 6]. Cells in CTC clusters can enter and exit the bloodstream more efficiently [7], are resistant to anoikis [6], and form up to 50-times more tumors as compared to CTCs that have undergone a complete EMT and move individually [6]. In addition, the implications of hybrid E/M phenotype in metastasis might help explain recent studies [8, 9] showing that preventing cells from switching to being fully mesenchymal does not drastically affect metastasis [10]. Furthermore, the predominance of cells co-expressing E and M markers in many aggressive tumors such as melanomas and basal-like and claudin-low breast cancers argues for a strong association of the hybrid E/M phenotype with aggressiveness [5]. Such co-expression, as compared to the expression of M genes only, correlates with increased invasive and metastatic potential and predicts poor outcomes independent of the breast cancer subtype [11]. Thus, the hybrid E/M phenotype can pose a higher metastatic risk in patients as compared to the pure M, i.e. complete EMT phenotype [5, 11].

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Epithelial-Mesenchymal Transition in tumor microenvironment

Epithelial-Mesenchymal Transition in tumor microenvironment

Wnt/b-caternin and Notch pathway are also emerging as important regulators of EMT in carcinoma cell lines, as well as the maintenance of stemness properties of stem cells. Translocation of b -caternin to the nuclear might result in the loss of E-cadherin to induce EMT, and b -caternin signaling is also essential to maintain the stemness properties of CSCs in skin cancer [63]. Trans- forming growth factor (TGF)- b , canonical and noncano- nical Wnt signaling all collaborated to induce activation of the EMT program and thereafter function in an auto- crine fashion to maintain the resulting mesenchymal state [64]. Inhibition of Wnt signaling can block EMT transcription factors and promote epithelial differentia- tion. Recent studies propose Snail2 as a target of Notch signaling, which is one of EMT transcription factors [65]. Blocking the Notch pathway by pharmacologic inhibitors of c-secretase might result in a depletion of CD133 stem-like cells in embryonal brain tumors [66]. Both the two signaling pathways contribute to EMT and to cancer stem-like cell characteristics in tumorigenesis.

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Search | Preprints

Search | Preprints

Metastasis remains the major cause of cancer-related deaths [1]. To enable successful metastasis, cancer cells often engage a trans-differentiation program referred to as epithelial-mesenchymal transition (EMT) in order to promote migratory and invasive properties [2]. During EMT, cells gradually lose epithelial features such as a cobblestone-like morphology, cell-cell adhesion and apico-basal polarity and acquire mesenchymal features such as a spindle-like morphology, increased motility and invasiveness [2]. The concept of EMT was initially described during embryonic development. EMT was first observed in vitro by Greenberg and Hay showing that epithelial cells suspended in three-dimensional collagen gels lose their apical-basal polarity and acquire characteristics of migrating mesenchymal cells [3]. Later in vivo work by Nieto et al. argued that EMT is essential for the formation of mesoderm and the generation of the migratory neutral crest cells during chicken embryonic development [4]. EMT also plays a critical role during physiological wound repair and pathological fibrosis [5]. In the context of cancer metastasis, EMT has been proposed to be typically associated with enhanced metastatic potential of cancer cells [2] and the reverse process - mesenchymal-epithelial transition (MET) – has been considered to facilitate effective metastatic colonization by regaining epithelial and proliferative traits that are lost during EMT [6].

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mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells

mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells

Airway epithelium presents all components of the cho- linergic system, namely muscarinic receptors, ChAT, high- affinity choline uptake, esterase, as well as ACh itself [15,16]. Recently, it was demonstrated that ACh regulates aspects of inflammation and remodeling through its ac- tion on AChRs during airway diseases [17-19]. Incubation of lung epithelial cells with ACh resulted in the release of inflammatory mediators. The secretion of these mediators was inhibited by tiotropium, a novel muscarinic antagonist [20]. In epithelial cells derived from COPD patients and smokers, ACh induced a significantly higher release of the inflammatory mediator LTB4 compared to control cells. This release of the lipid mediator was blocked by anti- cholinergic treatment as well [21]. In a COPD model of LPS-induced airway inflammation and remodeling in guinea pigs, tiotropium abrogated the LPS-induced in- crease in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on em- physema [22]. These results suggested that endogenous acetylcholine plays a major role in the pathogenesis of this disease. EMT takes center stage as the convergence point between inflammation and airway diseases. Inflammatory mediators are known to induce downregulation of epithe- lial cell–cell adhesion and promote mesenchymal gene ex- pression both in vitro and in vivo, and consequently inflammatory mediators have emerged as decisive factors in EMT induction. Although a number of molecules in- volved in ACh-mediated airway inflammation and remo- deling have been identified, little is known regarding the role of ACh in EMT.

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Embryonic mammary signature subsets are activated in Brca1 /  and basal like breast cancers

Embryonic mammary signature subsets are activated in Brca1 / and basal like breast cancers

was found to be activated predominantly in ER-negative breast cancers, including all 13 basal-like tumors, all five HER2-positive tumors, and four (13%) of 30 Luminal B tumors (Figure 3A, B). Another small basal-like tumor- associated subset was composed of genes encoding cell- cycle and microtubule cytoskeleton components, sug- gesting significant overlap with proliferation signatures, a general hallmark of poor-prognosis breast cancers [32] (see Additional file 4). The embryonic mammary epithe- lium displays a relatively low proliferation index at E12.5, but Ki67 + epithelial cells can be detected at this stage (Figure 3C). Three other subsets of the embryonic mammary epithelial signature are activated in many non-basal-like tumor types (Figure 3B). One cluster acti- vated predominantly in luminal tumors and repressed in most basal-like tumors consists of genes regulating neu- ron-projection development (Additional file 4). Two other clusters are activated in some luminal and HER2 + tumors and are enriched for genes involved in embryo- nic appendage morphogenesis, ossification, regionaliza- tion, negative regulation of macromolecule synthesis, and wound response (Additional file 4). The stability of the gene clusters was assessed with pvClust (see Addi- tional file 5). Of 57 genes activated in basal-like breast cancers, 55 are found in one of the two major clusters, which have robustness indices larger than 95%. Network analysis suggests complex genetic regulatory potential, and interacting associations exist between the proteins encoded by embryonic genes found activated and repressed in breast cancers (Figure 3D).

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Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective

Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective

In contrast to the limited progress in finding the causes of HLHS, there has been a revolution in our understanding of cardiac morphogenesis since the de- scription of the second heart field (SHF) in 2001. The previous theory proposing segmental patterning within the primitive heart tube was an attractive one, not least because it apparently explained many heart defects in- cluding HLHS. We now know it to be incorrect. Instead, it is recognised that a single atrial and ventricular cham- ber are initially formed from the first heart field (FHF), but that consequent addition of cells from the surround- ing SHF produce parts of the atria, the right ventricle and the outflow tract (reviewed in [18]). Studies using knockout and transgenic mice have indicated the im- portance of other multipotent progenitor populations in forming the heart including: neural crest cells; mesen- chymal cells formed by endothelial to mesenchymal transformation (EndoMT); smooth muscle cells and fi- broblasts derived by epithelial to mesenchymal trans- formation (EMT) from the epicardium (reviewed in [19]). It is an appropriate moment, therefore, to re- evaluate HLHS from a developmental perspective.

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The progression of epithelial-mesenchymal transformation in gliomas

The progression of epithelial-mesenchymal transformation in gliomas

Epithelial-mesenchymal transformation(EMT) was first observed in breast cancer in 1890s. Zhang J. et al. found that the EMT and mesenchymal-to-epithelial transition (MET, its reverse process), were reduplicative and alter- natively occurred in chicken’s epithelial cells [1]. In the recent 30 years, EMT becomes a hot research field and is generally divided into three different subtypes [2]. While type 1 EMT takes effect in the process of embry- onic development and differentiation. Type 2 EMT mainly appears in the process of adult inflammation and tissue repair in the condition of wound healing and organ fibrosis. Type 3 EMT is active in tumorigenesis, involving the acquisition of new phenotype, enhance- ment of motility and lose of the original morphology, and also a diversified dynamic process regulated by multiple factors [3].

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Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

Abstract: Proliferative vitreoretinopathy (PVR) is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF)-β2-induced epithelial-to-mesenchymal transition (EMT) plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1) and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and sup- pressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the preven- tion of PVR.

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Original Article MiR-211 inhibits cell epithelial-mesenchymal transition by targeting MMP9 in gastric cancer

Original Article MiR-211 inhibits cell epithelial-mesenchymal transition by targeting MMP9 in gastric cancer

lated in GC cell compared with the expression in GES-1 cells (Figure 1C). Furthermore, we found that up-regula- tion of miR-211 suppressed the cells invasion ability compared with miR-NC group in SGC-7901 and BGC-823 cells (Figure 2A-D). Moreover, we detected the association between miR-211 expression and EMT in GC cells. The results showed that up-regulation of miR-211 in SGC-7901 and BGC-823 cells led to relatively higher mRNA and protein levels of E-cadherin, but down- regulated transcription factors Twist1 and related markers N-cadherin in SGC-7901 and BGC-823 cells (Figure 3A-D). Thus, these results showed th- at miR-211 suppressed cell invasion and epithelial-mesenchymal transition (EMT) in GC cells.

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Expression of zinc finger transcription factors (ZNF143 and ZNF281) in serous borderline ovarian tumors and low-grade ovarian cancers

Expression of zinc finger transcription factors (ZNF143 and ZNF281) in serous borderline ovarian tumors and low-grade ovarian cancers

important role of ZNFs in initiation and progression of carcinogenesis. The zinc finger family includes both tumor suppressor genes and oncogenes [26, 27]. ZNFs are in- volved in all major pathways of cancer progression, from carcinogenesis to metastasis formation. Moreover, acting as transcription factors, they play a role in cancer develop- ment. Finally, a growing body of evidence suggests that zinc finger proteins may act as recruiters of chromatin modifiers or structural proteins that regulate the migra- tion and invasion of cancer cells. Increased cellular motil- ity is a key determinant of cancer progression, enabling migration, invasion and formation of metastases. Other processes playing a key role in the initiation and progres- sion of ovarian malignancies may also depend, at least in part, on the interaction between different types of com- mitted stem cells within the ovary and surrounding micro- environment [28]. Upregulation of pro-inflammatory cytokines, which is typical for ovulation, may contribute to creation of a local microenvironment which favors transformation of normal ovarian epithelial cells within the ovary; subsequently, the transformed ovarian epithelial cells may undergo immunoediting which orchestrates the interaction between infiltrating immune cells and ovarian stromal microenvironment toward EOC progression [29]. In our present study, we found the expressions of ZNF143 and ZNF 281 in 90 and 57% of examined specimens, re- spectively. This implies that both borderline ovarian tu- mors and low-grade ovarian cancers may undergo extensive processes associated with EMT initiation. Meta- static spread is a primary determinant of poor prognosis in cancer patients, and EMT plays a key role in cancer invasion and metastasis formation [30]. Based on the in- tensity of ZNF143 and ZNF 281 expressions in serous bor- derline tumors and low-grade ovarian cancers, one may hypothesize that metastasis formation and spread of these malignancies involve some additional, yet unidentified,

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<p>KGF Is Delivered to Inflammatory and Induces the Epithelial Hyperplasia in Trinitrobenzene Sulfonic Acid-Induced Ulcerative Colitis Rats</p>

<p>KGF Is Delivered to Inflammatory and Induces the Epithelial Hyperplasia in Trinitrobenzene Sulfonic Acid-Induced Ulcerative Colitis Rats</p>

Mesenchymal stem cells (MSCs) have the characteris- tics of low immunogenicity, anti-in fl ammatory, tissues repair that can also sense changes in environmental signals and migrate to in fl ammatory tissues. 3 MSCs have been found to be easily transfected with foreign genes and stably expressed recently. 4 The original MSCs have short- comings such as short survival time and low concentration of injury sites after implantation into the host, while genetically modi fi ed MSCs can overcome the above defects. 5 The preparation of stem cells expressing multiple cytokine modi fi cations by genetic engineering technology has been used for cell transplantation therapy, which also provides new ideas and prospects for the treatment of UC. 6 Keratinocyte growth factor (KGF), which is also known as fi broblast growth factor (FGF)-7, has a wide range of cytokine activity. 7 KGF is derived from MSCs that plays an important role in the repair of various organs such as the gastrointestinal, thymus, lung, and kidney. 8 Studies have con fi rmed that KGF can promote the recov- ery of epithelial function after small bowel resection, and the use of KGF gene therapy can signi fi cantly alleviate UC. 9 It has recently been reported that KGF can promote epithelial differentiation of MSCs in vitro, 10 suggesting that KGF may have some autocrine effects on MSCs themselves. Yao et al 11 reported that KGF-pretreated MSCs can be transplanted into the lung tissue of rats with pulmonary fi brosis injury to improve lung injury and fi brosis. Additionally, Yang et al 12 also found that KGF can enhance the repair of spinal cord injury in rats by MSCs transplantation. Based on these fi ndings, we hypothesized that KGF may enhance the therapeutic effects of MSCs on UC.

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