scholarly journals Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells

2010 ◽  
Vol 17 (1) ◽  
pp. 241-253 ◽  
Author(s):  
Frédéric R Santer ◽  
Kamilla Malinowska ◽  
Zoran Culig ◽  
Ilaria T Cavarretta
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Thymidine Incorporation ◽  
Proliferative Effect ◽  
Prostate Cells ◽  
Selective Targeting ◽  
Maspin Expression ◽  
And Migration ◽  
Different Content

Interleukin-6 (IL-6) is suggested to have a pathogenic role in the progression of prostate cancer (PC), therefore representing an attractive target for new therapies. However, due to the pleiotropy of this cytokine, targeting IL-6 results in different and unpredictable responses. In order to better understand the mechanisms underlying the different responses to the cytokine, we focused our attention on IL-6 receptors (IL-6Rs) that represent the first element in the cascade of cytokine-activated signalling pathways. IL-6 signal transduction may indeed occur through the membrane IL-6R (classical signalling) and/or through the less studied soluble IL-6R (sIL-6R; IL-6 trans-signalling (IL-6TS)). We provide the first evidence how responses to IL-6 may depend on the different content of IL-6Rs in PC. In particular, the studies of 3H-thymidine incorporation and exploitation of different approaches (i.e. activation or inhibition of IL-6TS in sIL-6R-negative and -positive cell lines and transfection of IL-6R siRNA) allowed us to demonstrate that IL-6TS specifically accounts for an anti-proliferative effect of the cytokine in three PC cell lines that are known to respond differently to IL-6. Additionally, by applying migration-, scratch- and adhesion assays, we show that IL-6TS increases motility and migration and decreases adhesion of prostate cells facilitating thereby processes that determine metastasis initiation and spread. Finally, by western analyses, we uncovered an IL-6- and sIL-6R-dependent downregulation of the tumour suppressor maspin. Collectively, these data suggest that selective targeting of IL-6TS might allow to refine the currently available experimental anti-IL-6 therapies against PC.

scholarly journals Amphiregulin-EGFR Autocrine Signaling Mediates Neutrophil Elastase-Triggered Prostate Cancer Progression

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1010-A1011
Author(s):  
Zhiguang Xiao ◽  
Stephen R Hammes
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Neutrophil Elastase ◽  
Dependent Manner ◽  
Prostate Cell ◽  
Erk Activation ◽  
Prostate Cells ◽  
Erk Phosphorylation

Abstract Neutrophil elastase (NE) is a serine protease stored in neutrophil azurophilic granules. Growing evidence indicates that NE is intimately involved in the activities of proinflammatory cytokines / chemokines, growth factors, and cell surface receptors. These molecular regulations can modulate innate immune responses as well as directly promote cancer cell outgrowth. To date, however, little is known regarding the molecular mechanisms underlying the stimulatory properties of NE in cancer cells. Here we examine NE effects on prostate cells, demonstrating that NE triggers proliferative signals and cell migration in six prostate cell lines representing the spectrum of prostate cell malignancy, including normal prostatic epithelium, benign prostatic hypertrophy, and metastatic prostate cancer. Using ERK activation as a read-out, we show that NE promotes ERK phosphorylation in a dose dependent manner, and time course study further reveal a sustained ERK activation upon NE treatment. Western blot evaluation demonstrates strong EGFR expression in cell lines derived from normal and benign prostatic gland, and preferential expression in hormone resistant versus hormone responsive cells. In agreement with EGFR-dependent mitogenic signaling, activation of ERK is abrogated by siRNA-mediated EGFR knockdown, as well as by pretreatment of cells with irreversible EGFR inhibitor AG1478. Importantly, NE evokes cancer cell migration at a lower range of NE concentrations relative to nonneoplastic cells. In prostate cells, from a total of seven EGFR ligands, amphiregulin (AREG) is predominantly expressed, and the addition of NE results in the release of AREG. Moreover, AREG gene silencing by siRNA or inhibition of AREG biological activity by neutralizing antibody, prevents NE-induced ERK phosphorylation and cell migration. Together, our study reveals a distinct and essential role of AREG-EGFR signaling axis in NE-triggered prostatic cellular response.

scholarly journals Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
M. Olivan ◽  
M. Rigau ◽  
E. Colás ◽  
M. Garcia ◽  
M. Montes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Lipid Lowering ◽  
Concomitant Treatment ◽  
Simultaneous Treatment ◽  
Invasion And Migration ◽  
Beneficial Effects ◽  
Increased Risk ◽  
And Migration

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812),P<0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155),P=0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939),P<0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effectsin vitroare enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence.

scholarly journals The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines

2019 ◽  
Vol 300 ◽  
pp. 63-72 ◽  
Author(s):  
Rossana Cocchiola ◽  
Mariangela Lopreiato ◽  
Raffaella Guazzo ◽  
Maria Margherita de Santi ◽  
Margherita Eufemi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines ◽  
Maspin Expression

scholarly journals The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4716-4726 ◽  
Author(s):  
Sumudra Periyasamy ◽  
Manya Warrier ◽  
Manoranjani P. M. Tillekeratne ◽  
Weinian Shou ◽  
Edwin R. Sanchez
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Cyclosporin A ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Lncap Cells ◽  
Androgen Ablation ◽  
Prostate Cells

The androgen receptor (AR) contributes to growth of prostate cancer even under conditions of androgen ablation. Thus, new strategies to target AR activity are needed. The AR interacts with the immunophilin FK506-binding protein 52 (FKBP52), and studies in the FKBP52 knockout mouse have shown that this protein is essential to AR activity in the prostate. Therefore, we tested whether the immunophilin ligand FK506 affected AR activity in prostate cancer cell lines. We also tested the hypothesis that the AR interacts with another immunophilin, cyclophilin 40 (Cyp40), and is regulated by its cognate ligand cyclosporin A (CsA). We show that levels of FKBP52, FKBP51, Cyp40, and a related co-chaperone PP5 were much higher in prostate cancer cells lines [(LNCaP), PC-3, and DU145] compared with primary prostate cells, and that the AR of LNCaP cells can interact with Cyp40. In the absence of androgen, CsA caused inhibition of cell growth in the AR-positive LNCaP and AR-negative PC-3 and DU145 cell lines. Interestingly, FK506 only inhibited LNCaP cells, suggesting a dependence on the AR for this effect. Both CsA and FK506 inhibited growth without inducing apoptosis. In LNCaP cells, CsA completely blocked androgen-stimulated growth, whereas FK506 was partially effective. Further studies in LNCaP cells revealed that CsA and FK506 were able to block or attenuate several stages of AR signaling, including hormone binding, nuclear translocation, and activity at several AR-responsive reporter and endogenous genes. These findings provide the first evidence that CsA and FK506 can negatively modulate proliferation of prostate cells in vitro. Immunophilins may now serve as new targets to disrupt AR-mediated prostate cancer growth.

scholarly journals LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8394 ◽  
Author(s):  
Wei Zhou ◽  
Kang Huang ◽  
Qiuyan Zhang ◽  
Shaojun Ye ◽  
Zibiao Zhong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Quantitative Polymerase Chain Reaction ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
And Migration

Background Aberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood. Methods LINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis. Results LINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1.

scholarly journals SPP1 Promotes Enzalutamide Resistance and EMT Activation in CRPC Progression via PI3K/AKT and ERK1/2 Pathways

2021 ◽  
Author(s):  
Xiaocong Pang ◽  
Junling Zhang ◽  
Xu He ◽  
Yanlun Gu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Strong Relationship ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Castration Resistant ◽  
And Migration

Abstract The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and anti-androgen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, metastatic levels in CRPC progression, and also investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity, and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, PCR, immunohistochemical staining and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC. SPP1 knockdown repressed enzalutamide sensitivity, invasion and migration of prostate cancer cells in vitro. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrate that SPP1 overexpression maintains the activation of PI3K/AKT signaling and ERK1/2 pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression, and help to discover new potential targets against mCRPC.

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