scholarly journals β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhibin Huang ◽  
Guihuan Li ◽  
Zhishuai Zhang ◽  
Ruonan Gu ◽  
Wenyang Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Chronic Stress ◽  
Metastatic Cancer ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
Emt Markers

Abstract Background Chronic stress is well known to promote tumor progression, however, little is known whether chronic stress-mediated regulation of osteoblasts contributes to the migration and invasion of metastatic cancer cells. Methods The proliferation, migration and invasion of prostate cancer cells were assessed by CCK-8 and transwell assay. HIF-1α expression of osteoblasts and epithelial-mesenchymal transition (EMT) markers of prostate cancer cells were examined by Western blot. The mRNA level of cytokines associated with bone metastasis in osteoblasts and EMT markers in PC-3 and DU145 cells were performed by qRT-PCR. Functional rescue experiment of cells were performed by using siRNA, plasmid transfection and inhibitor treatment. Results Isoproterenol (ISO), a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT, migration and invasion of PC-3 and DU145 cells, which could be inhibited by β2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. Conclusions These findings demonstrated that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

scholarly journals β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

2019 ◽  
Author(s):  
Zhibin Huang ◽  
Guihuan Li ◽  
Zhishuai Zhang ◽  
Ruonan Gu ◽  
Wenyang Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Chronic Stress ◽  
Adrenergic Receptor ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
And Migration

Abstract Background: Chronic stress is well known to promote tumor progression, however, little is known on whether neurotransmitters released after chronic stress induced sympathetic activation regulate the function of osteoblasts to affect migration and invasion of metastatic cancer cells. Methods: First, the changes in migration and invasion ability of prostate cancer cell lines PC-3 and DU145 were assessed by transwell migration assay. PC-3 and DU145 cells proliferation ability were detected by CCK-8, and HIF-1α expression of osteoblasts and the momentous proteins of epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells were examined by Western blot. Then, an analysis of the main cytokines associated with bone metastasis in osteoblasts and EMT-related biomarkers in PC-3 and DU145 cells was performed by qRT-PCR. Finally, rescue experiment was performed by using HIF-1α siRNA and inhibitor, HIF-1α overexpression plasmid, β2-adrenergic receptor (β2AR) inhibitor, CXCR4 siRNA and inhibitor. Results: In this study, isoproterenol (ISO), a non-selective β-adrenergic receptor (βAR) agonist, used as a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT and migration as well as invasion of PC-3 and DU145 cells, which was independent of promoting cell proliferation and could be inhibited by β2AR inhibitor. Mechanically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. Conclusions: These findings indicate that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

scholarly journals β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

2019 ◽  
Author(s):  
Zhibin Huang ◽  
Guihuan Li ◽  
Zhishuai Zhang ◽  
Ruonan Gu ◽  
Wenyang Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Chronic Stress ◽  
Adrenergic Receptor ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
And Migration

Abstract Background: Chronic stress is well known to promote tumor progression, however, little is known on whether neurotransmitters released after chronic stress induced sympathetic activation regulate the function of osteoblasts to affect migration and invasion of metastatic cancer cells. Methods: First, the changes in migration and invasion ability of prostate cancer cell lines PC-3 and DU145 were assessed by transwell migration assay. PC-3 and DU145 cells proliferation ability were detected by CCK-8, and HIF-1α expression of osteoblasts and the momentous proteins of epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells were examined by Western blot. Then, an analysis of the main cytokines associated with bone metastasis in osteoblasts and EMT-related biomarkers in PC-3 and DU145 cells was performed by qRT-PCR. Finally, rescue experiment was performed by using HIF-1α siRNA and inhibitor, HIF-1α overexpression plasmid, β2-adrenergic receptor (β2AR) inhibitor, CXCR4 siRNA and inhibitor. Results: In this study, isoproterenol (ISO), a non-selective β-adrenergic receptor (βAR) agonist, used as a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT and migration as well as invasion of PC-3 and DU145 cells, which was independent of promoting cell proliferation and could be inhibited by β2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. Conclusions: These findings indicate that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

scholarly journals β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

2019 ◽  
Author(s):  
Zhibin Huang ◽  
Guihuan Li ◽  
Zhishuai Zhang ◽  
Ruonan Gu ◽  
Wenyang Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Chronic Stress ◽  
Adrenergic Receptor ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
And Migration

Abstract Background Chronic stress is well known to promote tumor progression, however, the mechanisms that underlie the association of chronic stress with cancer metastasis remain elusive. Methods First, the changes in migration and invasion ability of prostate cancer cell lines PC-3 and DU145 were assessed by transwell migration assay. And HIF-1α expression of osteoblasts and the momentous proteins of epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells were examined by western blot. Then, an analysis of the main cytokines associated with bone metastasis was performed in osteoblasts by qRT-PCR. Finally, HIF-1α siRNA and inhibitor YC-1 were used to assess the reverse of isoproterenol (ISO)-induced changes of HIF-1α in osteoblasts, and β2-adrenergic receptor (β2AR) inhibitor ICI118,551 and CXCR4 inhibitor LY2510924 were used to antagonizes migration and invasion of PC-3 and DU145 cells induced by osteoblasts triggered by ISO. Results In this study, ISO, a non-selective β-adrenergic receptor (βAR) agonist, used as a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibits no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promote EMT and migration as well as invasion of PC-3 and DU145 cells, which can be inhibited by β2AR inhibitor. Mechanically, ISO increases the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, inhibiting CXCL12-CXCR4 signaling with LY2510924 blunts the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. Conclusions These findings indicate that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

Interleukin-6, Tumor Necrosis Factor-α Expression Levels in Prostate Cancer Tissues and Their Effects on Epithelial Interstitial Transformation, Migration and Invasion in Prostate Cancer Cells

2020 ◽  
Vol 10 (12) ◽  
pp. 1773-1779
Author(s):  
Desheng Li ◽  
Shanbin Zhang ◽  
Minfang Zuo ◽  
Xinming Hu ◽  
Shuming He
Keyword(s):  
Prostate Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Necrosis Factor

Background: To investigate the expression of Interleukin-6, Interleukin-6 in prostate cancer tissues and its effect on migration and evasiveness of cancer cells. Material and Methods: The releasing of Interleukin-6, Tumor necrosis factor-α in prostate cancer cells was detected by ELISA method. For prostate cancer cells after knockout, additional Interleukin-6 or Tumor necrosis factor-α induction was given in vitro. After 12 h of culture, the effects of Interleukin-6, Tumor necrosis factor-α on the migration and evasiveness of prostate cancer cells were observed by Western blot method and matrices invasion experiment. Results: The expression of epithelial mesenchymal transition-related proteins, the migration and invasion ability of prostate cancer cells in each gene knockout group were significantly reduced. After induction of inflammatory factors (Interleukin-6 or Tumor necrosis factor-α) in the gene knockout group for 12 h, the expression levels of epithelial mesenchymal transition-related proteins, the migration and aggressiveness of prostate cancer were significantly higher than those after knockout. Conclusion: Interleukin-6 and Tumor necrosis factor-α can induce epithelial mesenchymal transition in LNCaP and PC3 cells, promote cell invasion and metastasis, and provide a new direction for future research.

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.

MicroRNA-501-5p Targets PINX1 Gene to Regulate the Proliferation, Migration, and Invasion of Prostatic Carcinoma Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 471-477
Author(s):  
Yueguang Zhao ◽  
Xiaohua Zhang ◽  
Hao Ye ◽  
Zhixian Yu ◽  
Junhua Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Prostate Epithelial Cells ◽  
Du145 Cells ◽  
High Level

The expression of PINX1 is decreased in prostate cancer, and the high level of miRNA-501-5p promotes the proliferation of liver cancer cells. However, there is no relevant research on miRNA-501-5p in prostate cancer. miRNA-501-5p can target the 3’UTR of PINX1 mRNA; however, it is unclear whether they affect the migration, invasion, and proliferation of prostate cancer cells. In this paper, PCR and Western blot were used to detect the expression of miRNA-501-5p and PINX1 in prostate cancer cells PC3, LNCaP, and DU145, and normal prostate epithelial cells RWPE-1. Compared to the normal prostate epithelial cells, miRNA-501-5p expression in prostate cancer cells was increased, and the expression of PINX1 was decreased. The methyl thiazolyl tetrazolium assay was used to detect the migration, proliferation, and invasion of prostate cancer DU145 cells. It was found that suppressing the expression of miRNA-501-5p or overexpressing PINX1 could inhibit the proliferation and other biological behaviors of DU145 cells; at the same time, the level of Cyclin D1, MMP-2, and MMP-14 protein was decreased, and the protein level of P21 was increased. Moreover, inhibition of PINX1 expression could partially reverse miRNA-501-5p’s inhibitory effect on the migration, invasion, and proliferation of prostate cancer cells. Therefore, miRNA-501-5p targeted PINX1 for down-regulation to promote prostate cancer cell migration, invasion, and proliferation.

Sign in / Sign up

Export Citation Format

Share Document