Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment

Although prostate cancer is clinically manageable during the early stages of progression, metastatic progression severely compromises the prognosis and leads to mortality. Constitutive activation of STAT3 has been connected to prostate cancer malignancy, and abolishing the STAT3 activity may diminish tumor growth and metastasis. However, its suppressor genes and pathways have not been well established. In this study, we show that promyelocytic leukemia zinc finger (PLZF) has a putative tumor-suppressor function in prostate cancer by inhibiting phosphorylation of STAT3. Compared with a benign prostate, high-grade prostate cancer patient tissue was negatively correlated with PLZF expression. PLZF depletion accelerated proliferation and survival, migration, and invasion in human prostate cancer cells. Mechanistically, we demonstrated a novel role of PLZF as the transcriptional regulator of the tyrosine phosphatase SHP-1 that inhibits the oncogenic JAKs–STAT3 pathway. These results suggest that the collapse of PLZF expression by the CCL3 derived from fibroblasts accelerates the cell migration and invasion properties of prostate cancer cells. Our results suggest that increasing PLZF could be an attractive strategy for suppressing prostate cancer metastasis as well as for tumor growth.

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Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells

10.1101/2020.04.23.057778 ◽

2020 ◽

Author(s):

Sangryoung Park ◽

Ho-Yong Lee ◽

Hansol Park ◽

Young Seok Ju ◽

Jayoung Kim ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Cancer Metastasis ◽

Cavernous Malformation ◽

Predictive Biomarker ◽

Cerebral Cavernous Malformation ◽

Binding Motif ◽

Prostate Cancer Cells ◽

Prostate Cancer Metastasis

AbstractEnhanced Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling is correlated with the extraprostatic extension of prostate cancer. However, the mechanism by which YAP/TAZ signaling becomes hyperactive and drives prostate cancer progression is currently unclear. In this study, we demonstrated that CCM1 induces the metastasis of multiple types of prostate cancer cells by regulating YAP/TAZ signaling. Mechanistically, CCM1, a gene mutated in cerebral cavernous malformation, suppresses DDX5, which regulates the PLK1-mediated suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. We also revealed that higher expression of CCM1, which is uniquely found in advanced prostate cancer, is inversely correlated with metastasis-free and overall survival in patients with prostate cancer. Our findings highlight the importance of CCM1-DDX5-PLK1-YAP/TAZ signaling in the metastasis of prostate cancer cells.Statement of SignificanceOur analysis of CCM1 expression and function represents a candidate predictive biomarker for prostate cancer metastasis and provides an evidence that abnormality of CCM1 can be pathogenic in prostate cancer. Importantly, CCM1 regulation of metastasis progression appears to a common molecular event in metastatic prostate cancer cells arising in disparate genetic backgrounds.

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SFMBT2-Mediated Infiltration of Preadipocytes and TAMs in Prostate Cancer

Cancers ◽

10.3390/cancers12092718 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2718

Author(s):

Jungsug Gwak ◽

Hayan Jeong ◽

Kwanghyun Lee ◽

Jee Yoon Shin ◽

Taejun Sim ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Cancer Metastasis ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Down Regulation ◽

Low Level ◽

Potential Biomarker ◽

Prostate Cancer Metastasis

Infiltration of diverse cell types into tumor microenvironment plays a critical role in cancer progression including metastasis. We previously reported that SFMBT2 (Scm-like with four mbt domains 2) regulates the expression of matrix metalloproteinases (MMPs) and migration and invasion of cancer cells in prostate cancer. Here we investigated whether the down-regulation of SFMBT2 regulates the infiltration of preadipocytes and tumor-associated macrophages (TAMs) in prostate cancer. We found that the down-regulation of SFMBT2 promotes the infiltration of preadipocytes and TAMs through up-regulation of CXCL8, CCL2, CXCL10, and CCL20 expression in prostate cancer. Expression of CXCL8, CCL2, CXCL10, and CCL20 was also elevated in prostate cancer patients having a higher Gleason score (≥8), which had substantially lower SFMBT2 expression. We also found that the up-regulation of CXCL8, CCL2, CXCL10, and CCL20 expression is dependent on NF-κB activation in prostate cancer cells expressing a low level of SFMBT2. Moreover, increased IL-6 from infiltrated preadipocytes and TAMs promoted migration and invasion of prostate cancer cells expressing a low level of SFMBT2. Our study may suggest that SFMBT2 a critical regulator for the infiltration of preadipocytes and TAMs into the prostate tumor microenvironment. Thus, the regulation of SFMBT2 may provide a new therapeutic strategy to inhibit prostate cancer metastasis, and SFMBT2 could be used as a potential biomarker in prostate cancer metastasis.

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Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT

10.21203/rs.3.rs-78710/v1 ◽

2020 ◽

Author(s):

Yao Zhao ◽

Chenchen Cai ◽

Lubing Shi ◽

Jiwei Wang ◽

Miaomiao Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Metastasis ◽

Ectopic Expression ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Eph Receptor ◽

Prostate Cancer Metastasis

Abstract Background Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is still unclear. Methods We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. Results We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. Conclusions These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.

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An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nanoclay bone-mimetic scaffolds

MRS Advances ◽

10.1557/adv.2018.682 ◽

2019 ◽

Vol 4 (21) ◽

pp. 1207-1213 ◽

Cited By ~ 4

Author(s):

MD Shahjahan Molla ◽

Dinesh R. Katti ◽

Kalpana S. Katti

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Metastatic Prostate Cancer ◽

Cancer Metastasis ◽

Human Mesenchymal Stem Cells ◽

Culture Technique ◽

Complex Nature ◽

Bone Microenvironment ◽

Prostate Cancer Cells

ABSTRACTProstate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.

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UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction

Cancer Letters ◽

10.1016/j.canlet.2011.01.006 ◽

2011 ◽

Vol 302 (2) ◽

pp. 128-135 ◽

Cited By ~ 48

Author(s):

Min Jung Jang ◽

Sung Hee Baek ◽

Jung Hwa Kim

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Metastasis ◽

Prostate Cancer Cells

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Epithelial-to-mesenchymal transition involves triacylglycerol accumulation in DU145 prostate cancer cells

Molecular BioSystems ◽

10.1039/c5mb00413f ◽

2015 ◽

Vol 11 (12) ◽

pp. 3397-3406 ◽

Cited By ~ 24

Author(s):

Núria Dalmau ◽

Joaquim Jaumot ◽

Romà Tauler ◽

Carmen Bedia

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Crucial Role ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Biological Process ◽

Prostate Cancer Cells ◽

Mesenchymal Transition ◽

Triacylglycerol Accumulation

Epithelial to mesenchymal transition (EMT) is a biological process that plays a crucial role in cancer metastasis.

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Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway

Translational Andrology and Urology ◽

10.21037/tau.2020.03.02 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1013-1027

Author(s):

Qiliang Cai ◽

Yegang Chen ◽

Dingnrong Zhang ◽

Jiancheng Pan ◽

Zunke Xie ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Metastasis ◽

Prostate Cancer Cells ◽

Castration Resistant ◽

Tgf Β1

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Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells

Journal of Clinical Medicine ◽

10.3390/jcm8030354 ◽

2019 ◽

Vol 8 (3) ◽

pp. 354 ◽

Cited By ~ 6

Author(s):

Kouji Izumi ◽

Atsushi Mizokami

Keyword(s):

Prostate Cancer ◽

Cell Migration ◽

Androgen Receptor ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Metastasis ◽

Prostate Cancer Cell ◽

Standard Form ◽

Cancer Cell Migration ◽

Prostate Cancer Cells

Androgen/androgen receptor (AR) signaling is a significant driver of prostate cancer progression, therefore androgen-deprivation therapy (ADT) is often used as a standard form of treatment for advanced and metastatic prostate cancer patients. However, after several years of ADT, prostate cancer progresses to castration-resistant prostate cancer (CRPC). Androgen/AR signaling is still considered an important factor for prostate cancer cell survival following CRPC progression, while recent studies have reported dichotomic roles for androgen/AR signaling. Androgen/AR signaling increases prostate cancer cell proliferation, while simultaneously inhibiting migration. As a result, ADT can induce prostate cancer metastasis. Several C-C motif ligand (CCL)-receptor (CCR) axes are involved in cancer cell migration related to blockade of androgen/AR signaling. The CCL2-CCR2 axis is negatively regulated by androgen/AR signaling, with the CCL22-CCR4 axis acting as a further downstream mediator, both of which promote prostate cancer cell migration. Furthermore, the CCL5-CCR5 axis inhibits androgen/AR signaling as an upstream mediator. CCL4 is involved in prostate carcinogenesis through macrophage AR signaling, while the CCL21-CCR7 axis in prostate cancer cells is activated by tumor necrotic factor, which is secreted when androgen/AR signaling is inhibited. Finally, the CCL2-CCR2 axis has recently been demonstrated to be a key contributor to cabazitaxel resistance in CRPC.

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Transcription Factor HBP1 Enhances Radiosensitivity by Inducing Apoptosis in Prostate Cancer Cell Lines

Analytical Cellular Pathology ◽

10.1155/2016/7015659 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yicheng Chen ◽

Yueping Wang ◽

Yanlan Yu ◽

Liwei Xu ◽

Youyun Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Cancer Metastasis ◽

Expression Level ◽

Prostate Cancer Cells ◽

Expression Levels ◽

The Relationship

Radiotherapy for prostate cancer has been gradually carried out in recent years; however, acquired radioresistance often occurred in some patients after radiotherapy. HBP1 (HMG-box transcription factor 1) is a transcriptional inhibitor which could inhibit the expression of dozens of oncogenes. In our previous study, we showed that the expression level of HBP1 was closely related to prostate cancer metastasis and prognosis, but the relationship between HBP1 and radioresistance for prostate cancer is largely unknown. In this study, the clinical data of patients with prostate cancer was compared, and the positive correlation was revealed between prostate cancer brachytherapy efficacy and the expression level of HBP1 gene. Through research on prostate cancer cells in vitro, we found that HBP1 expression levels were negatively correlated with oncogene expression levels. Furthermore, HBP1 overexpression could sensitize prostate cancer cells to radiation and increase apoptosis in prostate cancer cells. In addition, animal model was employed to analyze the relationship between HBP1 gene and prostate cancer radiosensitivity in vivo; the result showed that knockdown of HBP1 gene could decrease the sensitivity to radiation of xenograft. These studies identified a specific molecular mechanism underlying prostate cancer radiosensitivity, which suggested HBP1 as a novel target in prostate cancer radiotherapy.

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