scholarly journals Epithelial-To-Mesenchymal Transition Markers and CD44 Isoforms Are Differently Expressed in 2D and 3D Cell Cultures of Prostate Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 143 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Michele Sommariva ◽  
Patrizia Limonta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Culture ◽  
Confocal Microscopy ◽  
Cell Cultures ◽  
Cd44 Isoforms ◽  
Mesenchymal Transition ◽  
3D Cell Cultures ◽  
3D Spheroids ◽  
E Cadherin

Three-dimensional (3D) cell cultures allow the mimic of functions of living tissues andprovide key information encoded in tissue architecture. Considered the pivotal role of epithelial-tomesenchymaltransition (EMT) in carcinoma progression, including prostate cancer (PCa), weaimed at investigating the effect of the 3D arrangement on the expression of some key markers ofEMT in cultured human prostate cancer (PCa) cells, to better understand PCa cell behavior. PC3 andDU145 PCa cells were cultured in RPMI cell culture medium either in 2D-monolayers or in 3Dspheroids.The main EMT markers E-cadherin, N-cadherin, α-smooth muscle actin (αSMA),vimentin, Snail, Slug, Twist and Zeb1 were evaluated by confocal microscopy, real-time PCR andWestern blot. Confocal microscopy revealed that E-cadherin was similarly expressed at the cellboundaries on the plasma membrane of PCa cells grown in 2D-monolayers, as well as in 3Dspheroids,but resulted up-regulated in 3D-spheroids, compared to 2D-monolayers, at the mRNAand protein level. Moreover, markers of the mesenchymal phenotype were expressed at very lowlevels in 3D-spheroids, suggesting important differences in the phenotype of PCa cells grown in 3Dspheroidsor in 2D-monolayers. Considered as a whole, our findings contribute to a clarification ofthe role of EMT in PCa and confirm that a 3D cell culture model could provide deeper insight intothe understanding of the biology of PCa.

scholarly journals Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Common Disease ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
Endothelial Growth Factor ◽  
E Cadherin

Abstract Background Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa. Methods Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected. Results miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis. Conclusions The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial–mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

scholarly journals Silencing Akt1 Inhibits Starvation Induced Lung Metastasis Through Epithelial Mesenchymal Transition Independent of E-cadherin in Prostate Cancer

2020 ◽  
Author(s):  
Mei Yang ◽  
Hui Liu ◽  
Guo Ping Qiu ◽  
Fei Gao
Keyword(s):  
Prostate Cancer ◽  
Lung Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Starvation Resistance ◽  
Mesenchymal Transition ◽  
Tail Vein Injection ◽  
Emt Markers ◽  
E Cadherin

Abstract BackgroundEpithelial to mesenchymal transition (EMT) of prostate cancer (PCa) cells facilitates their progress to metastasis. We have recently reported Akt1 is an important EMT regulator, and silencing Akt1 induced EMT and inhibited the growth of PCa cells. These results imply Akt1 silencing may increase starvation resistance of PCa cells. However, little is known about the role of Akt1 of PCa cells in starvation.MethodsApoptosis was detected by TUNEL and flow cytometry, cell invasion was detected by transwells and ECIS, lung metastasis was evaluated by tail vein injection animal model, variation of EMT markers was detected by Western-blot.ResultsWe found starvation slowed down the growth and proliferation, and increased apoptosis of PCa cells; Silencing Akt1 gene inhibited these effects of starvation and decreased E-cadherin. Akt1 silencing enhanced invasion induced by starvation of PCa cells in vitro ; however, it inhibited lung metastasis induced by starvation of PCa cells in vivo unexpectedly.ConclusionStarvation or silencing Akt1 alone can promote lung metastasis of PCa cells, however, silencing Akt1 while starving PCa cells can significantly inhibit this function via EMT independent of E-cadherin.

410: Cleavage of E-Cadherin and the Role of an 80KDa Fragment in the Metastatic Progression of Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 108-108
Author(s):  
Rainer Kuefer ◽  
Kathleen Day ◽  
Jonathan Rios-Doria ◽  
Matthias Hofer ◽  
Arul Chinnaiyan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Progression ◽  
E Cadherin

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.

scholarly journals Correction to: Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Inhibitory Role

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals The effects of IGF-I on prostate cancer progression and the influence of hyperglycaemia

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Rehanna Mansor ◽  
Jeff Holly ◽  
Claire Perks
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Blue Dye ◽  
Normal Prostate ◽  
Mesenchymal Transition ◽  
Igf I ◽  
Epithelial Marker ◽  
Du145 Cells ◽  
E Cadherin

Epithelial to mesenchymal transition (EMT) is a necessary process in the conversion of benign tumor to aggressive and highly invasive cancer. Dysregulation of the IGF system and impaired metabolic regulation have been implicated in the progression of prostate cancer. However, the mechanisms underlying these effects require further investigation. We used normal prostate epithelial cells PNT2 and DU145 prostate cancer cells. Western immunoblotting was used to determine changes in protein abundance. Trypan blue dye exclusion assay was employed to assess cell proliferation and transwell migration assays to assess cells migration. Under normal glucose conditions, IGF-I inhibited EMT in PNT2 cells demonstrated by an upregulation in the epithelial marker E-cadherin together with loss of mesenchymal markers; vimentin and fibronectin. In contrast to PNT2 cells, IGF-I induced EMT in DU145 cells, as shown by the reduction of E-cadherin level and upregulation of vimentin and fibronectin. We observed that exposure to hyperglycaemia (25mM glucose concentration) alone induced EMT in both PNT2 and DU145 cells. The changes in EMT markers induced by hyperglycaemia (loss of epithelial marker and increase of mesenchymal markers) associated with increased cell proliferation and migration.  In high glucose conditions, IGF-I was still able to inhibit EMT in PNT2 cells, whereas in DU145 cancer cells, the addition of IGF-I could not enhance EMT any further.  In conclusion, IGF-I and hyperglycaemia play important roles in promoting prostate cancer cell progression through the regulation of EMT programme.  

scholarly journals miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Krassimira Todorova ◽  
Diana Zasheva ◽  
Kristiyan Kanev ◽  
Soren Hayrabedyan
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Mesenchymal Transition ◽  
Cell Line Model ◽  
E Cadherin

Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.

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