Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and Jazz167 were more active in PC3 cells and DU145 cells in comparison to normal prostate cells (PNT1A) and showed a 2.45- and 1.30-fold selectivity and higher cytotoxicity toward DU145 cells, respectively. Jazz90 and Jazz167 reduced HDAC activity by ~60% at 50 nM in PC3 lysates. At 4 μM, Jazz90 and Jazz167 increased acetylation in PC3 cells by 6- to 8-fold. Flow cytometry studies on the cell phase distribution demonstrated that Jazz90 causes a G0/G1 arrest in AR-null cells, whereas Jazz167 leads to a G0/G1 arrest in DU145 cells. However, apoptosis only occurred at a maximum of 7% of the total cell population following compound treatments in PC3 and DU145 cells. There was a reduction in cyclin D1 and no significant changes in bcl-2 in DU145 and PC3 cells. Overall, the results showed that Jazz90 and Jazz167 function as cytostatic HDAC inhibitors in AR-null prostate cancer cells.

Download Full-text

AS1 expression in prostate cancer and its effects on proliferation and invasion of prostate cancer cells

Cancer Biomarkers ◽

10.3233/cbm-203021 ◽

2021 ◽

pp. 1-9

Author(s):

Yuxin Li ◽

Xiaohong Zhuang ◽

Li Zhuang ◽

Hongjian Liu

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Related Protein ◽

Prostate Cancer Cells ◽

Blank Group ◽

Normal Prostate ◽

Cell Cycles ◽

Prostate Cells ◽

Proliferation And Invasion

This paper aimed at investigating AS1 expression in prostate cancer (PCa) and its effects on the proliferation and invasion of prostate cancer cells (PCCs). The prostate tissues and the matched adjacent normal prostate tissues excised and preserved during radical prostatectomy in our hospital were collected. The LncRNA NCK1-AS1 expression was detected. PCa patients were followed up for three years to analyze their prognosis. The correlation of LncRNA NCK1-AS1 expression with clinicopathological features was analyzed. Human normal prostate cells and human PCCs were selected, in which LncRNA NCK1-AS1 expression was tested to screen and then transfect the cells. Cell proliferation, invasion and migration were detected. Cell cycles and apoptosis were analyzed. Compared with the adjacent normal tissues, LncRNA NCK1-AS1 was highly expressed in the prostate cancer tissues. Its expression was remarkably different in those with different stages of TNM and with lymphatic metastasis or not. The prognosis of patients with high LncRNA NCK1-AS1 expression was remarkably poorer than that of those with low expression. Compared with the human normal prostate cells, LncRNA NCK1-AS1 expression in the human PCCs remarkably rose, with the greatest difference in 22Rv1 cells. Compared with the Blank group, cell proliferation and the number of plate cloned cells remarkably reduced in the sh-NCK1-AS1 group. Additionally, in this group, the number of invasive and migratory cells remarkably reduced; the expression of invasion-related protein E-cadherin remarkably rose but that of MMP-2 remarkably reduced; cell cycles were arrested and the expression of cycle-related proteins (CDK4, CDK6, cyclin D1) remarkably reduced; the apoptotic rate and the expression of apoptosis-related protein Bax remarkably rose. LncRNA NCK1-AS1 is highly expressed in PCa, so its down-regulation can inhibit PCCs from proliferating and reduce the number of invasive cells.

Download Full-text

Proteolytic fragments of fibronectin function as matrikines driving the chemotactic affinity of prostate cancer cells to human bone marrow mesenchymal stromal cells via the α5β1 integrin

Cell Adhesion & Migration ◽

10.1080/19336918.2016.1212139 ◽

2016 ◽

Vol 11 (4) ◽

pp. 305-315 ◽

Cited By ~ 10

Author(s):

Raghav Joshi ◽

Edi Goihberg ◽

Wenying Ren ◽

Monika Pilichowska ◽

Paul Mathew

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Cells ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Prostate Cancer Cells ◽

Α5β1 Integrin

Download Full-text

eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1

BMC Cancer ◽

10.1186/s12885-021-08749-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qi Li ◽

Mulun Xiao ◽

Yibo Shi ◽

Jinhao Hu ◽

Tianxiang Bi ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Translation Initiation ◽

Genetic Alterations ◽

Cell Counting ◽

Migration And Invasion ◽

Cell Group ◽

Prostate Cancer Cells ◽

Normal Prostate

Abstract Background Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study. Methods In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR (qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo. Results Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells. Conclusion eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.

Download Full-text

Dissociated Primary Human Prostate Cancer Cells Coinjected with the Immortalized Hs5 Bone Marrow Stromal Cells Generate Undifferentiated Tumors in NOD/SCID-γ Mice

PLoS ONE ◽

10.1371/journal.pone.0056903 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56903 ◽

Cited By ~ 9

Author(s):

Xin Chen ◽

Bigang Liu ◽

Qiuhui Li ◽

Sofia Honorio ◽

Xin Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Cells ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Undifferentiated Tumors

Download Full-text

Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500830 ◽

2018 ◽

Vol 46 (07) ◽

pp. 1625-1643 ◽

Cited By ~ 3

Author(s):

Hung-En Chen ◽

Ji-Fan Lin ◽

Te-Fu Tsai ◽

Yi-Chia Lin ◽

Kuang-Yu Chou ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Allyl Isothiocyanate ◽

Beclin 1 ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Normal Prostate ◽

Autophagy Induction ◽

Pc3 Cells

Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals, inhibits the survival of human prostate cancer cells while minimally affecting normal prostate epithelial cells. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging from the increased level of LC3-II protein in a dose- and time-dependent manner, but not in the normal prostate epithelial cell (PrEC). Inhibition of autophagy in AITC-treated cells decreased cell viability and enhanced apoptosis, suggesting that the autophagy played a protective role. There are several pathways activated in ATIC-treated cells. We detected the phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK activation were also detected. However, inhibition of AITC-activated ERK, AMPK and JNK by pre-treatment of specific inhibitors did not alter autophagy induction. Finally, increased beclin-1 expression was detected in AITC-treated cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction, indicating that AITC-induced autophagy occurs through upregulating beclin-1. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through upregulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in prostate cancer patients.

Download Full-text

Abstract 521: Active sonic hedgehog signaling between androgen independent human prostate cancer cells and normal/benign but not cancer-associated prostate stromal cells

10.1158/1538-7445.am2011-521 ◽

2011 ◽

Author(s):

Katsumi Shigemura ◽

Wen-chin Haung ◽

Haiyen Zhau ◽

Xiangyan Li ◽

Masuo Yamashita ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Sonic Hedgehog ◽

Stromal Cells ◽

Hedgehog Signaling ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Sonic Hedgehog Signaling ◽

Androgen Independent

Download Full-text

SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/β-catenin signaling

Cellular & Molecular Biology Letters ◽

10.1186/s11658-019-0195-4 ◽

2019 ◽

Vol 24 (1) ◽

Cited By ~ 4

Author(s):

Qiang Fu ◽

Zhenye Sun ◽

Fan Yang ◽

Tianci Mao ◽

Yanyao Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Target Gene ◽

Prostate Cancer Cell ◽

Luciferase Reporter ◽

Prostate Cancer Cells ◽

Normal Prostate ◽

Proliferation And Invasion ◽

In Cells

Abstract Background Sex-determining region Y-box containing gene 30 (SOX30) is a newly identified tumor-associated gene in several types of cancer. However, whether SOX30 is involved in the development and progression of prostate cancer remains unknown. This study investigated the potential role of SOX30 in prostate cancer. Methods Prostate cancer cell lines and a normal prostate epithelial cell line were used for the experiments. The expression of SOX30 was determined using quantitative real-time PCR and western blot analysis. The malignant cellular behaviors of prostate cancer were assessed using the Cell Counting Kit-8, colony formation and Matrigel invasion assays. The miRNA–mRNA interaction was validated using the dual-luciferase reporter assay. Results SOX30 expression was lower in cells of prostate cancer lines than in cells of the normal prostate epithelial line. Its overexpression repressed the proliferation and invasion of prostate cancer cells. SOX30 was identified as a target gene of microRNA-653-5p (miR-653-5p), which is upregulated in prostate cancer tissues. MiR-653-5p overexpression decreased SOX30 expression, while its inhibition increased SOX30 expression in prostate cancer cells. MiR-653-5p inhibition also markedly restricted prostate cancer cell proliferation and invasion. SOX30 overexpression or miR-653-5p inhibition significantly reduced β-catenin expression and downregulated the activation of Wnt/β-catenin signaling. SOX30 knockdown significantly reversed the miR-653-5p inhibition-mediated inhibitory effect on the proliferation, invasion and Wnt/β-catenin signaling in prostate cancer cells. Conclusions These results reveal a tumor suppressive function for SOX30 in prostate cancer and confirmed the gene as a target of miR-653-5p. SOX30 upregulation due to miR-653-5p inhibition restricted the proliferation and invasion of prostate cancer cells, and this was associated with Wnt/β-catenin signaling suppression. These findings highlight the importance of the miR-653-5p–SOX30–Wnt/β-catenin signaling axis in prostate cancer progression.

Download Full-text

Effect of androgen signaling in stromal cells on growth of prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.297 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 297-297 ◽

Cited By ~ 3

Author(s):

Chun-Peng Liao ◽

Leng-Ying Chen ◽

Andrea Luethy ◽

Youngsoo Kim ◽

A. Robert MacLeod ◽

...

Keyword(s):

Prostate Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Stromal Cells ◽

Culture System ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Epithelial Cancer ◽

Mesenchymal Transition

297 Background: Interactions between epithelial and stroma cells are important in the development of prostate cancer (PCa). Cancer-associated fibroblasts (CAFs) have been to support tumor progression, metastasis, and differentiation. Androgen receptor (AR) and related pathways are known to support the growth and survival of prostate epithelial cancer cells, the roles of AR-dependent processes in cancerous stroma are less clear. We sought to investigate if AR-dependent pathways present in CAF cells influence the growth and tumorogencity of epithelial cancer cells in relation to androgen-deprivation therapy in prostate cancer. Methods: Murine CAFs were isolated from a well-described PTEN-dependent cancer mouse model (Liao, et al Cancer Res, 2010. 70(18):7294). A co-culture system was developed based on multiple lines of murine CAFs grown along with human prostate cancer epithelial cells, and a murine-specific anti-sense oligonucleotide (ASO) against murine AR was used to specifically suppress AR expression in murine CAFs in this system. RT-PCR was used to investigate changes in gene expression. Results: Using this co-culture system, we found that murine CAFs promoted cell proliferation and colony formation in several human prostate cancer cell lines. Further, these processes were decreased by suppression of AR-expression in CAFs. Expression of genes related to tumorigenicity in epithelial cells were investigated. Markers associated with epithelial-mesenchymal transition (EMT, N-Cad) and “stemness” (OCT4, Sox2, Nanog) were increased in human prostate cancer cells grown with low-AR CAFs. Conclusions: Our data indicates that suppression of AR in CAFs results in down-regulation in the growth and tumorigenicity of prostate cancer cells through pathways related to EMT and “cell reprograming”. As such, development of therapies which inhibit the tumor-promoting pathways present in stromal cells may be one approach to improve the treatment of prostate cancer.

Download Full-text