Proliferation of Mouse Prostate Cancer Cells Inflamed by Trichomonas vaginalis

Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.

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Overexpression of Glypican 5 (GPC5) Inhibits Prostate Cancer Cell Proliferation and Invasion via Suppressing Sp1-Mediated EMT and Activation of Wnt/β-Catenin Signaling

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15044461944385 ◽

2018 ◽

Vol 26 (4) ◽

pp. 565-572 ◽

Cited By ~ 17

Author(s):

Yu Sun ◽

Kai Xu ◽

Miao He ◽

Guilian Fan ◽

Hongming Lu

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Cancer Cell Proliferation ◽

Mesenchymal Transition ◽

The Family ◽

Signaling Activation ◽

Proliferation And Invasion

Glypican 5 (GPC5) belongs to the family of heparan sulfate proteoglycans (HSPGs). It was initially known as a regulator of growth factors and morphogens. Recently, there have been reports on its correlation with the tumorigenic process in the development of some cancers. However, little is known about its precise role in prostate cancer (PCa). In the present study, we explored the expression pattern and biological functions of GPC5 in PCa cells. Our results showed that GPC5 was lowly expressed in PCa cell lines. Upregulation of GPC5 significantly inhibited PCa cell proliferation and invasion in vitro as well as attenuated tumor growth in vivo. We also found that overexpression of GPC5 inhibited the epithelial‐mesenchymal transition (EMT) and Wnt/β-catenin signaling activation, which was mediated by Sp1. Taken together, we suggest GPC5 as a tumor suppressor in PCa and provide promising therapeutic strategies for PCa.

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Involvement of Macrophages in Proliferation of Prostate Cancer Cells Infected with Trichomonas vaginalis

The Korean Journal of Parasitology ◽

10.3347/kjp.2021.59.6.557 ◽

2021 ◽

Vol 59 (6) ◽

pp. 557-564

Author(s):

Kyu-Shik Kim ◽

Hong-Sang Moon ◽

Sang-Su Kim ◽

Jae-Sook Ryu

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cell Line ◽

Conditioned Medium ◽

Trichomonas Vaginalis ◽

Cytokine Receptor ◽

Cytokine Receptors ◽

Mrna Levels ◽

Prostate Cancer Cells ◽

Mouse Prostate

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.

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MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

Technology in Cancer Research & Treatment ◽

10.1177/1533033821989817 ◽

2021 ◽

Vol 20 ◽

pp. 153303382198981

Author(s):

Xin-bo Sun ◽

Yong-wei Chen ◽

Qi-sheng Yao ◽

Xu-hua Chen ◽

Min He ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Viability ◽

Cell Apoptosis ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Mesenchymal Transition ◽

Proliferation And Apoptosis ◽

High Incidence ◽

Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

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N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer

Endocrine Related Cancer ◽

10.1677/erc-10-0015 ◽

2010 ◽

Vol 17 (2) ◽

pp. 469-479 ◽

Cited By ~ 79

Author(s):

Karin Jennbacken ◽

Tajana Tešan ◽

Wanzhong Wang ◽

Heléne Gustavsson ◽

Jan-Erik Damber ◽

...

Keyword(s):

Prostate Cancer ◽

Epithelial Mesenchymal Transition ◽

Neuroendocrine Differentiation ◽

Hormonal Treatment ◽

Androgen Deprivation ◽

Prostate Tumors ◽

Primary Tumors ◽

Mesenchymal Transition ◽

Molecular Alterations

Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial–mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.

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Wogonoside Inhibits Prostate Cancer Cell Growth and Metastasis via Regulating Wnt/β-Catenin Pathway and Epithelial-Mesenchymal Transition

Pharmacology ◽

10.1159/000502400 ◽

2019 ◽

Vol 104 (5-6) ◽

pp. 312-319 ◽

Cited By ~ 1

Author(s):

Can Wei ◽

Junfeng Jing ◽

Yanbin Zhang ◽

Ling Fang

Keyword(s):

Prostate Cancer ◽

Cell Viability ◽

Epithelial Mesenchymal Transition ◽

Phase Cell ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Pc3 Cells ◽

Gsk 3Β

Background: Wogonoside, an effective component of Scutellaria baicalensis extract, has recently become a hot topic for its newly discovered anticancer efficacy, but the underlying pharmacological mechanism is still unclear. In this study, we tested the inhibitory effects of wogonoside in human prostate cancer PC3 cells in vitro and vivo. Methods: The effects of wogonoside on cell viability, cycle progression, invasion, migration, and apoptosis were assessed in vitro. The levels of proteins in related signaling pathways were detected by western blotting assay. Finally, nude mouse tumorigenicity assay was conducted to detect the anticancer effect of wogonoside in vivo. Results: Wogonoside inhibited cell viability, invasive and migratory ability in a time- and dose-dependent manner. Flow cytometry indicated that wogonoside could induce cell apoptosis and S phase cell-cycle arrest. Mechanically, wogonoside suppressed the Wnt/β-catenin signaling pathway, and the level of p-glycogen synthase kinase-3β (GSK-3β; Ser9) was inhibited by wogonoside. The epithelial-mesenchymal transition (EMT) process was also reversed in PC3 cell line after wogonoside treatment. In vivo experiments showed that wogonoside inhibited tumor growth in xenograft mouse models. Conclusion: These findings revealed that wogonoside could suppress Wnt/β-catenin pathway and reversing the EMT process in PC3 cells. GSK-3β acts as a tumor suppressor in prostate cancer. Wogonoside may serve as an effective agent for treating prostate cancer.

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Elevated Expression Levels of PC3-Secreted Microprotein (PSMP) in Prostate Cancer Associated With Increased Xenograft Growth and Modification of Immune-Related Microenvironment

Frontiers in Oncology ◽

10.3389/fonc.2019.00724 ◽

2019 ◽

Vol 9 ◽

Author(s):

Xiaolei Pei ◽

Danfeng Zheng ◽

Shaoping She ◽

Zhiwei Fang ◽

Shiying Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Neutralizing Antibodies ◽

Epithelial Mesenchymal Transition ◽

Macrophage Polarization ◽

Xenograft Model ◽

Metastatic Progression ◽

Male Mortality ◽

Mesenchymal Transition ◽

Monocyte Migration

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PC3-secreted microprotein (PSMP) in PCa tumor tissues with high Gleason scores. According to biopsy results, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial–mesenchymal transition (EMT) of PC3 in vitro. Additionally, PSMP could also influence cytokine production in the xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, providing an effective option to cure human PCa.

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Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14685034103392 ◽

2016 ◽

Vol 24 (5) ◽

pp. 381-389 ◽

Cited By ~ 7

Author(s):

Feng Jiang ◽

Yan Shi ◽

Hong Lu ◽

Guojun Li

Keyword(s):

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Mesenchymal Transition ◽

Armadillo Repeat ◽

Proliferation And Invasion

Armadillo repeat-containing protein 8 (ARMC8) plays an important role in regulating cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. However, the expression pattern and role of ARMC8 in osteosarcoma are still unclear. In this study, our aims were to examine the effects of ARMC8 on osteosarcoma and to explore its underlying mechanism. Our results demonstrated that ARMC8 was overexpressed in osteosarcoma cell lines. Knockdown of ARMC8 significantly inhibited osteosarcoma cell proliferation in vitro and markedly inhibited xenograft tumor growth in vivo. ARMC8 silencing also suppressed the epithelial‐mesenchymal transition (EMT) phenotype, as well as inhibited the migration and invasion of osteosarcoma cells. Furthermore, knockdown of ARMC8 obviously inhibited the expression of β-catenin, c-Myc, and cyclin D1 in MG-63 cells. In conclusion, this report demonstrates that ARMC8 silencing inhibits proliferation and invasion of osteosarcoma cells. Therefore, ARMC8 may play an important role in the development and progression of human osteosarcoma and may represent a novel therapeutic target in the treatment of osteosarcoma.

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SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.678967 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhao-Ming Xiao ◽

Dao-Jun Lv ◽

Yu-zhong Yu ◽

Chong Wang ◽

Tao Xie ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Cycle Progression ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

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Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells

Biology ◽

10.3390/biology9030052 ◽

2020 ◽

Vol 9 (3) ◽

pp. 52 ◽

Cited By ~ 1

Author(s):

Elif Damla Arisan ◽

Ozge Rencuzogullari ◽

Ines Lua Freitas ◽

Syanas Radzali ◽

Buse Keskin ◽

...

Keyword(s):

Prostate Cancer ◽

Epithelial Mesenchymal Transition ◽

Significant Inhibition ◽

Developmentally Regulated ◽

Tissue Samples ◽

Mesenchymal Transition ◽

Formalin Fixed Paraffin ◽

Signaling Axis

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

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MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

Cellular Physiology and Biochemistry ◽

10.1159/000464120 ◽

2017 ◽

Vol 41 (3) ◽

pp. 1135-1146 ◽

Cited By ~ 36

Author(s):

Yang Du ◽

Xiu-heng Liu ◽

Heng-cheng Zhu ◽

Lei Wang ◽

Jin-zhuo Ning ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

In Vivo Studies ◽

Mesenchymal Transition ◽

Proliferation And Metastasis

Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.

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