Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

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BackgroundProteomics may help us better understand the changes of multiple proteins involved in oncogenesis and progression of prostate cancer(PCa) and identify more diagnostic and prognostic biomarkers. The aim of this study was to screen biomarkers of PCa by the proteomics analysis using isobaric tags for relative and absolute quantification(iTRAQ).MethodsThe patients undergoing prostate biopsies were classified into 3 groups according to pathological results: benign prostate hyperplasia (BPH, n = 20), PCa(n = 20) and BPH with local prostatic intraepithelial neoplasm(PIN, n = 10). Then, all the specimens from these patients were analyzed by iTRAQ and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS). The Gene Ontology(GO) function and the transcription regulation networks of the differentially expressed were analyzed by MetaCore software. Western blotting and Immunohistochemical staining were used to analyze the interesting proteins.ResultA total of 760 proteins were identified from 13787 distinct peptides, including two common proteins that enjoy clinical application: prostate specific antigen (PSA) and prostatic acid phosphatase(PAP). Proteins that expressed differentially between PCa and BPH group were further analyzed. Compared with BPH, 20 proteins were significantly differentially up-regulated (>1.5-fold) while 26 were significantly down-regulated in PCa(<0.66-fold). In term of GO database, the differentially expressed proteins were divided into 3 categories: cellular component(CC), molecular function (MF) and biological process(BP). The top 5 transcription regulation networks of the differentially expressed proteins were initiated through activation of SP1, p53, YY1, androgen receptor(AR) and c-Myc The overexpression of periostin in PCa was verified by western blotting and immunohistochemical staining.ConclusionOur study indicates that the iTRAQ technology is a new strategy for global proteomics analysis of the tissues of PCa. A significant up-regulation of periostin in PCa compared to BPH may provide clues for not only a promising biomarker for the prognosis of PCa but also a potential target for therapeutical intervention.

Prostate cancer is the second most common malignancy in men and androgen deprivation therapy is the first-line therapy. However, most cases will eventually develop castration-resistant prostate cancer after androgen deprivation therapy treatment. Enzalutamide is a second-generation androgen receptor antagonist approved by the Food and Drug Administration to treat patients with castrationresistant prostate cancer. Unfortunately, patients receiving enzalutamide treatment will ultimately develop resistance via various complicated mechanisms. This review examines the emerging information on these resistance mechanisms, including androgen receptor-related signalling pathways, glucocorticoid receptor-related pathways and metabolic effects. Notably, lineage plasticity and phenotype switching, gene polymorphisms and the relationship between microRNAs and drug resistance are addressed. Furthermore, potential therapeutic strategies for enzalutamideresistant castration-resistant prostate cancer treatment are suggested, which can help discover more effective and specific regimens to overcome enzalutamide resistance.

Combination immunotherapy is a promising strategy to remove the inhibitory effect of the tumor microenvironment on immune effector cells, improving the efficacy of immune checkpoint inhibitor treatment in bladder cancer. However, it is challenging to deliver multiple drugs to the tumor tissue effectively and simultaneously to ensure optimal therapeutic effects. Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1). The tumor-targeting, biosafety, and therapeutic effects of these nanocomplexes (AB680@EMVs-aPDL1), as a combined immunotherapy strategy for bladder cancer, were assessed in vitro and in vivo. Our results indicate that the nanodrug system was highly stable, provided adequate biosafety, and enhanced tumor targeting in a mouse model of bladder cancer. Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.

HER-2 positivity is prognostic for predicting progression to muscle invasion in NMIBC. Combination of the high-risk factors with HER-2 expression is more valuable for determining which NMIBC is more aggressive.

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