RelB promotes the migration and invasion of prostate cancer DU145 cells via exosomal ICAM1 in vitro

2021 ◽  
pp. 110221
Author(s):  
Wenjing Li ◽  
Jingjing Xu ◽  
Li Cheng ◽  
Chenyi Zhao ◽  
Lianjun Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Migration And Invasion ◽  
Du145 Cells

Cleaved High Molecular Weight Kininogen (HKa) and Kininostatin (D5) Induce Apoptosis and Inhibit Migration and Invasion of Human Prostate Cancer Cells by Preventing AKT Phosphorylation and Cyclin D1 Synthesis and Disrupting the Interaction of UPAR and EGFR.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 405-405
Author(s):  
Yuchuan Liu ◽  
Robin Pixley ◽  
Mario Fusaro ◽  
Robert W. Colman
Keyword(s):  
Prostate Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Plasma Kallikrein ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Du145 Cells

Abstract Tumor metastasis is a major factor in the mortality rate in human prostate cancer. Upregulation and activation of EGFR and/or uPAR in a variety of cancers have been shown to be associated with poor prognosis. HK, a component of the plasma kallikrein-kinin system, can be hydrolyzed by plasma kallikrein to bradykinin and HKa. HKa and D5 both have been demonstrated to have potent anti-angiogenic activity in vitro and in vivo. We previously published that D5 directly inhibits human colon carcinoma cell (HCT-116) proliferation in vitro by blocking the G1/S transition in the cell cycle. We now show that HKa [100 nM] inhibits the migration of human prostate tumor cell (DU145) about 50%. Cyclin D1 can activate p21 and p27 with concomitant cell migration. DU145 cells rapidly increase cyclin D1 synthesis in response to bFGF [1.2 nM]. HKa suppresses cyclin D1 expression as shown by Western blotting as well as cell immunoflourescence. Stimulation by bFGF or VEGF results in clustering of uPAR and EGFR on the surface of DU145 cells. Immunoflourescence shows that the addition of HKa disrupts the co-localization of uPAR and EGFR. HKa or a monoclonal antibody against uPAR decreases the phosphorylation of EGFR at Tyr 1173. The phosphorylation of ERK and AKT, which are downstream effectors of EGFR, is also inhibited by HKa. Kininostatin [300nM] induced apoptosis of human prostate cancer cells challenged with uPA [50 nM] or EGF [6.7 nM]. Matrigel invasion assay reveals that HKa [100 nM] decreases the invading cell number by 90%. These novel data indicate that HKa and kininostatin induce apoptosis and inhibit migration and invasion of human prostate cancer cells, indicating the therapeutic potential of kininostatin in metastasis human prostate cancer.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

scholarly journals Anticancer activity of midostaurin in hormone refractory human prostate cancer DU145 cells

2016 ◽  
Vol 11 (2) ◽  
pp. 378
Author(s):  
Jin-Jun Sun ◽  
Shi-Feng Kan ◽  
Guan-Xing Sun
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitor ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Nerve Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Du145 Cells ◽  
Hormone Refractory

<p class="Abstract">We tried a new method of prostate cancer treatment by inducing<em> in vitro</em> differentiation which resulted in reduction of cancer cells growth. A protein kinase inhibitor, midostaurin's ability to trigger the human prostate cancer cell line, DU145 to segregate into nerve cells was studied. Midostaurin (100 nM) suppressed the growth of DU145 cells but without change in the number of dead cells. Midostaurin started to extend neurites on DU145 cells after 24 hours and differentiated into nerve cells by 72 hours. The microtubule was stabilized by tau protein and its mRNA expression showed time-dependent increase in midostaurin-treated DU145 cells. At the same time, the amount of acetylcholinesterase was also increased. The midostaurin-treated DU145 cells showed 40% less activity than control in the colony forming assay. The results suggests that midostaurin can induce differentiation of DU145 cells into nerve cells.</p><p> </p>

scholarly journals LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Enhui Ma ◽  
Qianqian Wang ◽  
Jinhua Li ◽  
Xinqi Zhang ◽  
Zhenjia Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Novel Target

Abstract Background Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet. Methods RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified. Results LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression. Conclusions LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.

scholarly journals Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

2019 ◽  
Vol 8 (12) ◽  
pp. 2056 ◽  
Author(s):  
Juan M. Jiménez-Vacas ◽  
Enrique Gómez-Gómez ◽  
Antonio J. Montero-Hidalgo ◽  
Vicente Herrero-Aguayo ◽  
Fernando L-López ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Xenograft Model ◽  
Grey Zone ◽  
Pathophysiological Role ◽  
Expression Activity ◽  
Du145 Cells

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.

scholarly journals Inhibition of LOXL2 Enhances the Radiosensitivity of Castration-Resistant Prostate Cancer Cells Associated with the Reversal of the EMT Process

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Peng Xie ◽  
Hongliang Yu ◽  
Feijiang Wang ◽  
Feng Yan ◽  
Xia He
Keyword(s):  
Prostate Cancer ◽  
Cell Apoptosis ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Du145 Cells ◽  
Androgen Independent

Introduction. Radiotherapy is the mainstay in the treatment of prostate cancer. However, significant radioresistance of castration-resistant prostate cancer (CRPC) cells constitutes a main obstacle in the treatment of this disease. By using bioinformatic data mining methods, LOXL2 was found to be upregulated in both androgen-independent prostate cancer cell lines and radioresistant tumor samples collected from patients with prostate cancer. We speculate that LOXL2 may play an important role in the radioresistance of CRPC cells. Methods. The effect of LOXL2 knockdown on the radiosensitivity of androgen-independent prostate cancer cells lines was measured by the clonogenic assay and xenograft tumor experiments under in vitro and in vivo conditions, respectively. In studies on the mechanism, we focused on the EMT phenotype changes and cell apoptosis changes induced by LOXL2 knockdown in DU145 cells. The protein levels of three EMT biomarkers, namely, E-cadherin, vimentin, and N-cadherin, were measured by western blotting and immunohistochemical staining. Cell apoptosis after irradiation was measured by flow cytometry and caspase-3 activity assay. Salvage experiment was also conducted to confirm the possible role of EMT in the radiosensitization effect of LOXL2 knockdown in CRPC cells. Results. LOXL2 knockdown in CRPC cells enhanced cellular radiosensitivity under both in vitro and in vivo conditions. A significant reversal of EMT was observed in LOXL2-silenced DU145 cells. Cell apoptosis after irradiation was significantly enhanced by LOXL2 knockdown in DU145 cells. Results from the salvage experiment confirmed the key role of EMT process reversal in the radiosensitization effect of LOXL2 knockdown in DU145 cells. Conclusions. LOXL2 plays an important role in the development of cellular radioresistance in CRPC cells. Targeting LOXL2 may be a rational avenue to overcome radioresistance in CRPC cells. A LOXL2-targeting strategy for CRPC treatment warrants detailed investigation in the future.

scholarly journals The Effects of Serum from Prostate Cancer Patients with Elevated Body Mass Index on Prostate Cancer Cells in Vitro

2015 ◽  
Vol 8 ◽  
pp. LPI.S23135
Author(s):  
Benjamin C. Mora ◽  
Neil E. Fleshner ◽  
Laurence H. Klotz ◽  
Vasundara Venkateswaran
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Obese Patients ◽  
Control Groups ◽  
Necrosis Factor Alpha ◽  
Pc3 Cells

We examined whether serum from obese, compared to non-obese, PCa (prostate cancer) patients creates a growth-enhancing tumor micro-environment in vitro. Serum from 80 subjects was divided into four groups: normal weight men with and without PCa and overweight/obese men with and without PCa. Cell proliferation, migration, and invasion were measured in LNCaP, and PC3 cells treated with patient serum were obtained from the above groups. The results reveal that proliferation of LNCaP cells was significantly ( P = 0.05) greater with serum from non-obese (mean = 1.26 ± 0.20) compared to that from obese patients (mean = 1.16 ± 0.19). Serum from obese PCa patients compared to non-obese PCa patients induced significantly greater amounts of cell migration ( P < 0.01) in PC3 cells. Serum from obese patients induced significantly ( P < 0.01) lower amounts of cell invasion (mean = 8.2 ± 4.5) compared to non-obese patients (mean = 18.1 ± 5.0) when treated on PC3 cells. Serum TNF-α (tumor necrosis factor alpha) levels correlated with LNCaP cell proliferation in vitro in non-obese PCa ( P < 0.01) and non-obese control groups ( P = 0.05). All statistical calculations controlled for age, since the PCa patient groups were significantly older than the control groups ( P < 0.01). In conclusion, serum from obese PCa patients induced greater PCa cell migration and lower cell proliferation and invasion in vitro.

scholarly journals Proteomic Profiling of Du145 Cell Line Exosomes Identifies Icam1 as Aputative molecular Mechanism by Which Relb Promotes The proliferation, Migration, and Invasion of Prostate cancer Cells

2020 ◽  
Author(s):  
Wenjing Li ◽  
Jingjing Xu ◽  
Li Cheng ◽  
Lianjun Zhang ◽  
Qiang Shao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Adhesion ◽  
Molecular Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Migration And Invasion ◽  
Label Free ◽  
Proteomic Profiling ◽  
Intercellular Adhesion Molecule 1 ◽  
Aggressive Phenotype ◽  
Du145 Cells

Abstract Background: Prostate cancer (PC) is a serious health issue in men. Exosome plays essential roles in modulating the oncogenesis and progression of PC. RelB is highly expressed in PC and plays oncogenic parts in DU145 cells. We aim to uncover the protein panel of exosomes derived from RelB-knockdown DU145 cells (siRelB) as compared to control cells (sictrl) and explore a potential mechanism that RelB conferring the more aggressive phenotype to DU145 cells.Methods: Exosomes derived from sictrl and siRelB were subjected to Liquid Chromatography-Mass Spectrometry for proteomics profiling. Label-free quantification strategy iBAQ (intensity-based absolute quantification) was used to quantify and Fold Change (FC) was calculated to identify the differentially expressed proteins (DEPs). The characterization of proteins was conducted by bioinformatics analysis. ICAM1 over-expressing DU145 cells (hICAM1) and control cells (hctrl) were established by transfection using Lipofectamine 2000. The cell growth, migration, and invasion capabilities were measured by the xCelligence real-time monitoring system. Annexin V/PI-staining was adopted to assess apoptosis. CCK-8 assay was applied for proliferation evaluation. Integrin β-1, MMP9, and uPA were detected by Western blot.Results: 1259 exosomal proteins were identified, with 160 and 105 proteins unique to the siRelB and sictrl, respectively, while 994 proteins were present in both. We identified 137 upregulated and 55 downregulated proteins in siRelB. Gene Ontology (GO) analysis revealed that some DEPs had the cell adhesion molecular activity and participated in the cell adhesion process. Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched that intercellular adhesion molecule-1 (ICAM1) was downregulated targeted by the NF-κB signaling. The FC of exosomal ICAM1 was 2.136. The expression of ICAM1 was positively related to RelB in PC by UALCAN. ICAM1 was shown to be co-expressed with RelB by GeneMANIA. The protein abundance of exosomal ICAM1 was lower in siRelB. hICAM1 had enhanced abilities of proliferation, migration, and invasion, with higher expression of Integrin β-1 when compared to hctrl.Conclusions: Our study identified 192 exosomal DEPs downstream of RelB in the DU145 cells. Exosomal ICAM1, conferring a more aggressive phenotype to DU145 cells, is a potential molecular mechanism modulating the tumorigenesis and progression of PC cells.

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