scholarly journals Prostate Cancer and Bone Metastases: The Underlying Mechanisms

2019 ◽  
Vol 20 (10) ◽  
pp. 2587 ◽  
Author(s):  
Sok Kuan Wong ◽  
Nur-Vaizura Mohamad ◽  
Tijjani Rabiu Giaze ◽  
Kok-Yong Chin ◽  
Norazlina Mohamed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cancer Cell Growth ◽  
Disease Manifestation ◽  
Receptor Activator ◽  
Parathyroid Hormone Related Peptide ◽  
Underlying Mechanisms ◽  
Skeletal Fracture

Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.

scholarly journals Circulating Prostate Tumor Cells Detected by Reverse Transcription-PCR in Men with Localized or Castration-Refractory Prostate Cancer: Concordance with CellSearch Assay and Association with Bone Metastases and with Survival

2009 ◽  
Vol 55 (4) ◽  
pp. 765-773 ◽  
Author(s):  
Pauliina Helo ◽  
Angel M Cronin ◽  
Daniel C Danila ◽  
Sven Wenske ◽  
Rita Gonzalez-Espinoza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Healthy Volunteers ◽  
Real Time ◽  
Tumor Cells ◽  
Reverse Transcription ◽  
Specific Antigen ◽  
Rt Pcr ◽  
Reverse Transcription Pcr ◽  
Pcr Assays

Abstract Background: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival. Methods: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch™; Veridex) approved for clinical use. Results: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (≥80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%–85%) and correlated (Kendall τ, 0.60–0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status. Conclusions: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.

scholarly journals Multifaced roles of PLAC8 in cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Misha Mao ◽  
Yifan Cheng ◽  
Jingjing Yang ◽  
Yongxia Chen ◽  
Ling Xu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Molecular Function ◽  
Cancer Cell Growth ◽  
The Impact ◽  
Functional Output

AbstractThe role of PLAC8 in tumorigenesis has been gradually elucidated with the development of research. Although there are common molecular mechanisms that enforce cell growth, the impact of PLAC8 is varied and can, in some instances, have opposite effects on tumorigenesis. To systematically understand the role of PLAC8 in tumors, the molecular functions of PLAC8 in cancer will be discussed by focusing on how PLAC8 impacts tumorigenesis when it arises within tumor cells and how these roles can change in different stages of cancer progression with the ultimate goal of suppressing PLAC8-relevant cancer behavior and related pathologies. In addition, we highlight the diversity of PLAC8 in different tumors and its functional output beyond cancer cell growth. The comprehension of PLAC8’s molecular function might provide new target and lead to the development of novel anticancer therapies.

Circulating tumor cells as a marker of bone metastases in patients with high-risk prostate cancer

2017 ◽  
Vol 16 (3) ◽  
pp. e617
Author(s):  
W.A. Cieślikowski ◽  
A. Ida ◽  
M. Hrab ◽  
J. Budna ◽  
M. Świerczewska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

scholarly journals Nuclear localization of parathyroid hormone-related peptide confers resistance to anoikis in prostate cancer cells

2012 ◽  
Vol 19 (3) ◽  
pp. 243-254 ◽  
Author(s):  
Serk In Park ◽  
Laurie K McCauley
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Nuclear Localization ◽  
Molecular Mechanisms ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Related Peptide ◽  
Parathyroid Hormone Related Peptide

Prostate cancer remains a leading cause of cancer-related death in men, largely attributable to distant metastases, most frequently to bones. Despite intensive investigations, molecular mechanisms underlying metastasis are not completely understood. Among prostate cancer-derived factors, parathyroid hormone-related peptide (PTHrP), first discovered as an etiologic factor for malignancy-induced hypercalcemia, regulates many cellular functions critical to tumor growth, angiogenesis, and metastasis. In this study, the role of PTHrP in tumor cell survival from detachment-induced apoptosis (i.e. anoikis) was investigated. Reduction ofPTHLH(encoding PTHrP) gene expression in human prostate cancer cells (PC-3) increased the percentage of apoptotic cells when cultured in suspension. Conversely, overexpression of PTHrP protected prostate cancer cells (Ace-1 and LNCaP, both typically expressing low or undetectable basal PTHrP) from anoikis. Overexpression of nuclear localization signal (NLS)-defective PTHrP failed to protect cells from anoikis, suggesting that PTHrP-dependent protection from anoikis is an intracrine event. A PCR-based apoptosis-related gene array showed that detachment increased expression of theTNFgene (encoding the proapoptotic protein tumor necrosis factor-α) fourfold greater in PTHrP-knockdown PC-3 cells than in control PC-3 cells. In parallel,TNFgene expression was significantly reduced in PTHrP-overexpressing LNCaP cells, but not in NLS-defective PTHrP overexpressing LNCaP cells, when compared with control LNCaP cells. Subsequently, in a prostate cancer skeletal metastasis mouse model, PTHrP-knockdown PC-3 cells resulted in significantly fewer metastatic lesions compared to control PC-3 cells, suggesting that PTHrP mediated antianoikis events in the bloodstream. In conclusion, nuclear localization of PTHrP confers prostate cancer cell resistance to anoikis, potentially contributing to prostate cancer metastasis.

scholarly journals Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Baotong Zhang ◽  
Yixiang Li ◽  
Qiao Wu ◽  
Lin Xie ◽  
Benjamin Barwick ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Advanced Prostate Cancer ◽  
Paracrine Signaling ◽  
Mesenchymal Phenotype ◽  
Cxcr4 Signaling ◽  
Metastatic Lesions ◽  
Underlying Mechanisms

AbstractAdvanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.

scholarly journals Resveratrol Suppresses Ovarian Cancer Cell Growth and Invasion Through Upregulation of microRNA-34a

2020 ◽  
Author(s):  
Bing Wei ◽  
Shangli Yao ◽  
Ming Gao ◽  
Zujun Wang ◽  
Wenyan Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Molecular Mechanisms ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Anti Cancer ◽  
Underlying Mechanisms

Abstract Resveratrol (RES), a natural compound found in red wine, has previously reported to suppress ovarian cancer (OC) cell growth in vitro and in vivo; however, its potential molecular mechanisms are not fully elucidated. The aim of this study is to investigate the suppressive potential of RES in OC cell growth and invasion and reveal the underlying mechanisms. Herein, we found that RES treatment obviously suppressed the proliferative and invasive capacities of OC cells, and elevated cell apoptosis in vitro. Subsequent microarray and qRT-PCR analysis further showed that microRNA-34a (miR-34a) was significantly increased by RES treatment. Moreover, the inhibitory effects of RES on OC cells were enhanced by miR-34a overexpression, whereas weakened by miR-34a inhibition in OC cells. Of note, Bcl-2, an anti-apoptotic gene, was identified as a direct target of miR-34a. Then, we revealed that RES decreased the expression of Bcl-2 in OC cells in a dose dependent manner. Furthermore, the anti-tumor effects of RES were abolished by overexpression of Bcl-2 in OC cells. Overall, these results demonstrated that RES exerts the anti-cancer effects on OC cells through the miR-34a/Bcl-2 axis.

scholarly journals Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology

2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Domenico D’Amario ◽  
Massimiliano Camilli ◽  
Stefano Migliaro ◽  
Francesco Canonico ◽  
Mattia Galli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Response ◽  
Multimodality Imaging ◽  
Long Term Outcomes ◽  
Disease Manifestation ◽  
Therapeutic Implications ◽  
Differential Gene ◽  
Underlying Mechanisms

Abstract Purpose of Review The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine. Recent Findings In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms. Summary Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.

scholarly journals Airway Microbiota as a Modulator of Lung Cancer

2020 ◽  
Vol 21 (9) ◽  
pp. 3044 ◽  
Author(s):  
Taichiro Goto
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Bacterial Toxins ◽  
Inflammatory Factors ◽  
Lung Carcinogenesis ◽  
Airway Microbiome ◽  
Underlying Mechanisms

Recent research on cancer-associated microbial communities has elucidated the interplay between bacteria, immune cells, and tumor cells; the bacterial pathways involved in the induction of carcinogenesis; and their clinical significance. Although accumulating evidence shows that a dysbiotic condition is associated with lung carcinogenesis, the underlying mechanisms remain unclear. Microorganisms possibly trigger tumor initiation and progression, presumably via the production of bacterial toxins and other pro-inflammatory factors. The purpose of this review is to discuss the basic role of the airway microbiome in carcinogenesis and the underlying molecular mechanisms, with the aim of developing anticancer strategies involving the airway microbiota. In addition, the mechanisms via which the microbiome acts as a modulator of immunotherapies in lung cancer are summarized.

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