scholarly journals The Role of S100A4 for Bone Metastasis in Prostate Cancer Cells

2020 ◽  
Author(s):  
Bongjun Kim ◽  
Haemin Kim ◽  
Suhan Jung ◽  
Jun-Oh Kwon ◽  
Min-Kyong Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cell Surface Receptor ◽  
Prostate Cancer Cells ◽  
S100a4 Protein ◽  
Knock Down ◽  
Pc3 Cells

Abstract Background: Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells.Methods: In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells.Results: The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion: Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.

scholarly journals The role of S100A4 for bone metastasis in prostate cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bongjun Kim ◽  
Suhan Jung ◽  
Haemin Kim ◽  
Jun-Oh Kwon ◽  
Min-Kyoung Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cell Surface Receptor ◽  
Prostate Cancer Cells ◽  
S100a4 Protein ◽  
Knock Down ◽  
Pc3 Cells

Abstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.

scholarly journals Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222812 ◽  
Author(s):  
Wenbo Zhang ◽  
Cheng Hu ◽  
Xiaojie Wang ◽  
Shanshan Bai ◽  
Subing Cao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Methylseleninic Acid ◽  
Induction Of Apoptosis

scholarly journals Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells

2019 ◽  
Vol 448 ◽  
pp. 155-167 ◽  
Author(s):  
Bethtrice Elliott ◽  
Ana Cecilia Millena ◽  
Lilya Matyunina ◽  
Mengnan Zhang ◽  
Jin Zou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Essential Role ◽  
Prostate Cancer Cells

scholarly journals A Comprehensive Analysis of FUT8 Overexpressing Prostate Cancer Cells Reveals the Role of EGFR in Castration Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 468 ◽  
Author(s):  
Naseruddin Höti ◽  
Tung-Shing Lih ◽  
Jianbo Pan ◽  
Yangying Zhou ◽  
Ganglong Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Growth Factor Receptor ◽  
Androgen Deprivation ◽  
Cell Surface Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Prostate Cancer Cells

The emergence of castration-resistance is one of the major challenges in the management of patients with advanced prostate cancer. Although the spectrum of systemic therapies that are available for use alongside androgen deprivation for treatment of castration-resistant prostate cancer (CRPC) is expanding, none of these regimens are curative. Therefore, it is imperative to apply systems approaches to identify and understand the mechanisms that contribute to the development of CRPC. Using comprehensive proteomic approaches, we show that a glycosylation-related enzyme, alpha (1,6) fucosyltransferase (FUT8), which is upregulated in CRPC, might be responsible for resistance to androgen deprivation. Mechanistically, we demonstrated that overexpression of FUT8 resulted in upregulation of the cell surface epidermal growth factor receptor (EGFR) and corresponding downstream signaling, leading to increased cell survival in androgen-depleted conditions. We studied the coregulatory mechanisms of EGFR and FUT8 expression in CRPC xenograft models and found that castration induced FUT8 overexpression associated with increased expression of EGFR. Taken together, our findings suggest a crucial role played by FUT8 as a mediator in switching prostate cancer cells from nuclear receptor signaling (androgen receptor) to the cell surface receptor (EGFR) mechanisms in escaping castration-induced cell death. These findings have clinical implication in understanding the role of FUT8 as a master regulator of cell surface receptors in cancer-resistant phenotypes.

scholarly journals Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shengjie Yu ◽  
Huihong Yu ◽  
Yuanfeng Zhang ◽  
Chuan Liu ◽  
Weili Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Cancer Cell Growth ◽  
Non Coding Rna ◽  
The Relationship ◽  
Long Non Coding Rna

Abstract Background Long non-coding RNA (lncRNA) has been confirmed to exert a critical effect on the progression of tumors, including prostate cancer. Previous literature has demonstrated LINC01116 involves in activities of multiple cancers. However, the underlying role of LINC01116 in prostate cancer remains unclear. Methods qRT-PCR measured the expression of LINC01116 in prostate cancer cells. EdU experiment was used to detect cell proliferation. Transwell assays detected cell migration and invasion. Immunofluorescence staining and western blot assays were utilized to measure EMT progress. The binding relationship between RNAs was confirmed by a series of mechanism assays. In addition, rescue experiments were conducted to verify the relationship among RNAs. Results LINC01116 was found to be highly expressed in prostate cancer cells. Functional assays indicated that inhibition of LINC01116 could suppress cell proliferation, migration, invasion and EMT progress. Also, miR-744-5p was proven to bind with LINC01116. Moreover, UBE2L3 was verified as the target gene of miR-744-5p. In rescue assays, we discovered that inhibited miR-744-5p or overexpressed UBE2L3 could offset the suppressive influence of silencing LINC01116 on prostate cancer cells. Conclusion Our study suggested that lncRNA LINC01116 acted as an oncogene in prostate cancer and accelerated prostate cancer cell growth through regulating miR-744-5p/UBE2L3 axis.

scholarly journals PHF19 mediated regulation of proliferation and invasiveness in prostate cancer cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Payal Jain ◽  
Cecilia Ballare ◽  
Enrique Blanco ◽  
Pedro Vizan ◽  
Luciano Di Croce
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Genes ◽  
Embryonic Stem ◽  
Prostate Cancer Cells ◽  
Genome Wide ◽  
A Genome ◽  
Matrix Organization

The Polycomb-like protein PHF19/PCL3 associates with PRC2 and mediates its recruitment to chromatin in embryonic stem cells. PHF19 is also overexpressed in many cancers. However, neither PHF19 targets nor misregulated pathways involving PHF19 are known. Here, we investigate the role of PHF19 in prostate cancer cells. We find that PHF19 interacts with PRC2 and binds to PRC2 targets on chromatin. PHF19 target genes are involved in proliferation, differentiation, angiogenesis, and extracellular matrix organization. Depletion of PHF19 triggers an increase in MTF2/PCL2 chromatin recruitment, with a genome-wide gain in PRC2 occupancy and H3K27me3 deposition. Transcriptome analysis shows that PHF19 loss promotes deregulation of key genes involved in growth, metastasis, invasion, and of factors that stimulate blood vessels formation. Consistent with this, PHF19 silencing reduces cell proliferation, while promotes invasive growth and angiogenesis. Our findings reveal a role for PHF19 in controlling the balance between cell proliferation and invasiveness in prostate cancer.

Association of cross-talk between α1D-adrenergic receptor (α1D -AR) and transient receptor potential vanilloid 1 (TRPV1) with the proliferation of PC3 prostate cancer cells.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 87-87
Author(s):  
Giorgio Santoni ◽  
Valerio Farfariello ◽  
Maria Beatrice Morelli ◽  
Sonia Liberati ◽  
Massimo Nabissi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cross Talk ◽  
Calcium Influx ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Proton Release ◽  
Trpv1 Receptors ◽  
Pc3 Cells

87 Background: Growing evidence supports the role of α1-ARs in the direct mitogenic effect of catecholamines on prostate cancer (PC) cell growth. The expression of α1D-AR on PC3 prostate cancer cells and the ability of noradrenalin (NA) to stimulate PC3 cell proliferation in a α1D-AR-dependent manner were reported (Quaglia et al., 2005). In addition, TRPV1 expression was also found in prostate cancers (Sanchez et al., 2006). Aim of this study was to investigate the relationship between α1D-AR and TRPV1 receptors and the involvement of TRPV1 in NA-induced proliferation in PC3 cells. Methods: By western blot analysis and confocal microscopy the expression α1D-AR and TRPV1 and localization in PC3 cells were evaluated. PC3 cells were incubated with NA alone or in combination with WS433 and capsazepine (CPZ), α1D-AR and TRPV1 antagonists. Proton release, calcium influx and cell proliferation were assessed in α1D-AR-, TRPV1- or α1D-AR/TRPV1 double-silenced PC3 cells by cytosensor and cytofluorymetric analyses. Finally, lysates from NA-treated PC3 cells alone or in combination with WS433 or CPZ were blotted with anti-phospho ERK, anti-ERK and anti-phospho-(Ser) PKC substrate Abs and Inositol-1,4,5-trisphosphate [3H] radioreceptor assay were performed. Results: α1D-AR and TRPV1 co-localize and are co-immunoprecipitated in PC3 cells. Treatment of PC3 cells with NA strongly stimulated proton release, calcium influx and cell proliferation that were reverted by α1D-AR WS433 and TRPV1 antagonist. NA-induced increase of survival and proliferation was totally abrogated in α1D-AR/TRPV1 silenced cells. In addition, NA stimulates ERK and PKC substrate phosphorylation that was inhibited by WS433 and CPZ. Finally, CPZ treatment inhibited NA-dependent PLC activation, while WS433 had no effect. Conclusions: A functional and structural cross-talk between α1D-AR and TRPV1 receptors control NA-induced proliferation of PC cells. These data strongly suggest the development of new pharmaceutical approaches based on bifunctional antibodies and molecules recognizing both α1D-AR and TRPV1 receptors.

scholarly journals 247: The Role of F70 S6K Pathways in the Progression to Androgen Independent Cell Proliferation in Prostate Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 68-68
Author(s):  
Takahiro Inoue ◽  
Eijiro Nakamura ◽  
Toru Yoshida ◽  
Yosuke Shimizu ◽  
Takehiko Segawa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Androgen Independent

scholarly journals Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 182
Author(s):  
Aya Misawa ◽  
Yukihiro Kondo ◽  
Hiroyuki Takei ◽  
Toshihiro Takizawa
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Osteoblastic Cells ◽  
Prostate Cancer Cells ◽  
Upstream Regulator ◽  
Chemokine Ligand ◽  
Pc3 Cells

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression, which play fundamental roles in cancer development. In this study, we found that homeobox A11 antisense RNA (HOXA11-AS), a highly expressed lncRNA in cell lines derived from prostate cancer bone metastases, promoted the cell invasion and proliferation of PC3 prostate cancer cells. Transcription factor homeobox B13 (HOXB13) was identified as an upstream regulator of HOXA11-AS.HOXA11-AS regulated bone metastasis-associated C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling in both PC3 prostate cancer cells and SaOS2 osteoblastic cells. The HOXB13/HOXA11-AS axis also regulated integrin subunits (ITGAV and ITGB1) specific to prostate cancer bone metastasis. HOXB13, in combination with HOXA11-AS, directly regulated the integrin-binding sialoprotein (IBSP) promoter. Furthermore, conditioned medium containing HOXA11-AS secreted from PC3 cells could induce the expression of CCL2 and IBSP in SaOS2 osteoblastic cells. These results suggest that prostate cancer HOXA11-AS and HOXB13 promote metastasis by regulation of CCL2/CCR2 cytokine and integrin signaling in autocrine and paracrine manners.

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