scholarly journals Urinary Extracellular Vesicles contain simplified transcriptomes enriched in circular & long noncoding RNAs with functional significance in prostate cancer

2021 ◽  
Author(s):  
anna Almeida ◽  
Marc Gabriel ◽  
Virginie Firlej ◽  
Lorena Martin-Jaular ◽  
Matthieu Lejars ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Phenotypic Characterization ◽  
Prostate Cell ◽  
Tumor Tissues ◽  
Dual Analysis ◽  
Protective Environment ◽  
Transcriptome Comparison ◽  
And Control

Abstract Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and anti-tumorigenic functions by controlling the immune response. In contrast to extracellular non-vesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and none have compared them with their tissue of origin. Here, we performed Total RNA-Sequencing on 6 Formaldehyde-Fixed-Parafilm-Embedded (FFPE) prostate cancer (PCa) tumor tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron-free cytoplasmic transcripts and specific lnc/circular (circ)RNAs, strikingly common to all patients. Our full cellular and EVs transcriptome comparison within 3 common PCa cell lines identified a set of overlapping 14 uEV-circRNAs characterized as essential for prostate cell proliferation in vitro and 15 uEV-lncRNAs that we predicted to encode 768 high-affinity neoantigens. Our dual analysis of EVs-lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV-lnc/circRNAs phenotypic characterization involved in PCa.

scholarly journals Prostate cancer urinary Extracellular Vesicles are enriched in cytoplasmic intron-free mRNAs and circular/long noncoding RNAs with functional significance

2021 ◽  
Author(s):  
anna Almeida ◽  
Marc Gabriel ◽  
Virginie Firlej ◽  
Lorena Martin-Jaular ◽  
Matthieu Lejars ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Phenotypic Characterization ◽  
Prostate Cell ◽  
Tumor Tissues ◽  
Dual Analysis ◽  
Protective Environment ◽  
Transcriptome Comparison ◽  
And Control

Abstract Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and anti-tumorigenic functions by controlling the immune response. In contrast to extracellular non-vesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and none have compared them with their tissue of origin. Here, we performed Total RNA-Sequencing on 6 Formaldehyde-Fixed-Parafilm-Embedded (FFPE) prostate cancer (PCa) tumor tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron-free cytoplasmic transcripts and specific lnc/circular (circ)RNAs, strikingly common to all patients. Our full cellular and EVs transcriptome comparison within 3 common PCa cell lines identified a set of overlapping 14 uEV-circRNAs characterized as essential for prostate cell proliferation in vitro and 15 uEV-lncRNAs that we predicted to encode 768 high-affinity neoantigens. Our dual analysis of EVs-lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV-lnc/circRNAs phenotypic characterization involved in PCa.

scholarly journals Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 40
Author(s):  
Hatice Bekci ◽  
Mustafa Cam ◽  
Ahmet Cumaoglu
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM).

scholarly journals Cancer Alters the Metabolic Fingerprint of Extracellular Vesicles

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3292
Author(s):  
Mari Palviainen ◽  
Kirsi Laukkanen ◽  
Zeynep Tavukcuoglu ◽  
Vidya Velagapudi ◽  
Olli Kärkkäinen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Western Blotting ◽  
Cell Metabolism ◽  
Cancer Cell Lines ◽  
Cancerous Cell ◽  
Metabolic Fingerprint ◽  
And Control

Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.

scholarly journals Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1495
Author(s):  
Egidia Costanzi ◽  
Rita Romani ◽  
Paolo Scarpelli ◽  
Ilaria Bellezza
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Target Cells ◽  
Prostate Cell ◽  
Prostate Cancer Therapy ◽  
Reverse Transcription Quantitative Pcr ◽  
Pc3 Cells

Prostate-derived extracellular vesicles (pEVs) may represent a way to selectively transport cargo molecules from the producing cells to the target cells to allow biological events, both in physiological and pathological circumstances. pEVs cargo participates in the modulation of the inflammatory responses in physiological conditions and during cancer progression. In the present study, we examined the expression levels of miRNA Let-7b, in both precursor and mature forms, in noncancerous and cancerous prostate cell lines, PNT2 and PC3 respectively, and in their extracellular vesicles (EVs) using reverse-transcription quantitative PCR strategies. We showed that miRNA Let-7b was highly expressed in noncancerous cells and strongly decreased in cancerous PC3 cells, while the opposite was observed in the respective EVs, thus supporting the tumor suppressor role of miRNA Let7-b. We also demonstrated that miRNA Let-7b can be transferred to THP-1 cells via EVs, which are known to induce TAM-like polarization. Our results support the view that miRNA Let-7 b, contained in PC3-derived EVs, is associated with the increase in the miRNA Let7-b observed in TAM-like macrophages. Overall, our results indicate that circulating EV-loaded miRNA might be useful biomarkers for prostate cancer progression and might also support a possible use of pEVs as targets for prostate cancer therapy.

scholarly journals In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues

2020 ◽  
Vol 13 (3) ◽  
pp. 47 ◽  
Author(s):  
Katarzyna B. Kaczor-Keller ◽  
Anna Pawlik ◽  
Jacek Scianowski ◽  
Agata Pacuła ◽  
Magdalena Obieziurska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Biological Activities ◽  
Cytotoxic Action ◽  
Organoselenium Compounds ◽  
M Cell ◽  
Normal Prostate ◽  
Prostate Cell ◽  
Anticancer Mechanism

Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.

scholarly journals Extracellular Vesicles in Prostate Cancer: New Future Clinical Strategies?

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ilaria Giusti ◽  
Vincenza Dolo
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Specific Antigen ◽  
Specific Marker ◽  
Cellular Origin ◽  
Organ Specific ◽  
Potential Use

Prostate cancer (PCa) is the most common cancer—excluding skin tumors—in men older than 50 years of age. Over time, the ability to diagnose PCa has improved considerably, mainly due to the introduction of prostate-specific antigen (PSA) in the clinical routine. However, it is important to take into account that although PSA is a highly organ-specific marker, it is not cancer-specific. This shortcoming suggests the need to find new and more specific molecular markers. Several emerging PCa biomarkers have been evaluated or are being assessed for their potential use. There is increasing interest in the prospective use of extracellular vesicles as specific markers; it is well known that the content of vesicles is dependent on their cellular origin and is strongly related to the stimulus that triggers the release of the vesicles. Consequently, the identification of a disease-specific molecule (protein, lipid or RNA) associated with vesicles could facilitate their use as novel biological markers. The present review describes severalin vitrostudies that demonstrate the role of vesicles in PCa progression and severalin vivostudies that highlight the potential use of vesicles as PCa biomarkers.

scholarly journals The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome

2020 ◽  
Vol 21 (4) ◽  
pp. 1303 ◽  
Author(s):  
Stefan Bauersachs ◽  
Pascal Mermillod ◽  
Carmen Almiñana
Keyword(s):  
Gene Expression ◽  
Extracellular Vesicles ◽  
Sequencing Analysis ◽  
Rna Seq ◽  
High Throughput Analysis ◽  
Positive Effects ◽  
Early Embryos ◽  
And Control ◽  
The Impact

Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo–oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of embryonic gene expression, the transcriptomes of embryos supplemented with bovine fresh (FeEVs) or frozen (FoEVs) oEVs during in vitro culture compared to controls without oEVs were analyzed by low-input RNA sequencing. Analysis of RNA-seq data revealed 221 differentially expressed genes (DEGs) between FoEV treatment and control, 67 DEGs for FeEV and FoEV treatments, and minor differences between FeEV treatment and control (28 DEGs). An integrative analysis of mRNAs and miRNAs contained in oEVs obtained in a previous study with embryonic mRNA alterations pointed to direct effects of oEV cargo on embryos (1) by increasing the concentration of delivered transcripts; (2) by translating delivered mRNAs to proteins that regulate embryonic gene expression; and (3) by oEV-derived miRNAs which downregulate embryonic mRNAs or modify gene expression in other ways. Our study provided the first high-throughput analysis of the embryonic transcriptome regulated by oEVs, increasing our knowledge on the impact of oEVs on the embryo and revealing the oEV RNA components that potentially regulate embryonic development.

Characterization of βARKct engineered extracellular vesicles and model specific cardioprotection

2021 ◽  
Author(s):  
Jin-Sook Kwon ◽  
Sarah M Schumacher ◽  
Erhe Gao ◽  
J Kurt Chuprun ◽  
Jessica Ibetti ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mouse Heart ◽  
Receptor Kinase ◽  
Embryonic Fibroblasts ◽  
Induced Apoptosis ◽  
And Control ◽  
G Protein Coupled

Recent data supporting any benefit of stem cell therapy for ischemic heart disease has suggested paracrine-based mechanisms via extracellular vesicles (EVs) including exosomes. We have previously engineered cardiac-derived progenitor cell (CDC) to express a peptide inhibitor, βARKct, of G protein-coupled receptor kinase 2, leading to improvements in cell proliferation, survival and metabolism. In this study we tested whether βARKct-CDC EVs would be efficacious when applied to stressed myocytes in vitro and in vivo. When isolated EVs from βARKct-CDC and control GFP-CDC were added to cardiomyocytes in culture, they both protected against hypoxia-induced apoptosis. We tested whether these EVs could protect the mouse heart in vivo following exposure either to myocardial infarction (MI) or acute catecholamine toxicity. Both types of EVs significantly protected against ischemic injury and improved cardiac function after MI compared to mice treated with EVs from mouse embryonic fibroblasts, however βARKct EVs treated mice did display some unique beneficial properties including significantly altered pro- and anti-inflammatory cytokines. Importantly, in a catecholamine toxicity model of heart failure (HF), myocardial injections of βARKct-containing EVs were superior at preventing HF compared to control EVs and this catecholamine toxicity protection was recapitulated in vitro. Therefore, introduction of the βARKct into cellular EVs can have improved reparative properties in the heart especially against catecholamine damage, which is significant since sympathetic nervous system activity is increased in HF.

scholarly journals Extracellular Vesicles from Human Advanced-Stage Prostate Cancer Cells Modify the Inflammatory Response of Microenvironment-Residing Cells

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1276 ◽  
Author(s):  
Letizia Mezzasoma ◽  
Egidia Costanzi ◽  
Paolo Scarpelli ◽  
Vincenzo Nicola Talesa ◽  
Ilaria Bellezza
Keyword(s):  
Prostate Cancer ◽  
Inflammatory Response ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Advanced Stage ◽  
Prostate Cell ◽  
Caspase 1 ◽  
Pc3 Cells

Prostate cancer (PCa) progression is strictly associated with microenvironmental conditions, which can be modified by cancer-released extracellular vesicles (EVs), important mediators of cell-cell communication. However, the role of EVs in the inflammatory cross-talk between cancer cells and microenvironment-residing cells remains largely unknown. To evaluate the role of EVs in the tumour microenvironment, we treated the non-cancerous prostate cell line PNT2 with EVs isolated from advanced-stage prostate cancer PC3 (PC3-EVs). Caspase-1-mediated IL-1β maturation was evaluated after 24 h incubation with EVs. Moreover, the effect of PC3-EVs on differentiated macrophagic THP-1 cells was assessed by analyzing cytokine expression and PC3 cells migration and proliferation profiles. We illustrated that PC3 cells contain active NLRP3-inflammasome cascade and secrete IL-1β. PC3-EVs affect the PNT2 inflammatory response, inducing caspase-1-mediated IL-1β maturation via ERK1/2-mediated lysosomal destabilization and cathepsin B activation. We also verified that PC3-EVs induce a functional TAM-like polarization in differentiated THP-1 cells. Our results demonstrated that cancer-derived EVs induce an inflammatory response in non-cancerous prostate cells, while inducing an immunomodulatory phenotype in immune cells. These apparently contradictory effects are both committed to strengthening the tumour-promoting microenvironment

scholarly journals Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 318
Author(s):  
Ben Lanning ◽  
Jason Webber ◽  
Pinar Uysal-Onganer ◽  
Wen Guo Jiang ◽  
Aled Clayton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Bone Cells ◽  
Large Degree ◽  
Extracellular Vesicle ◽  
Skeletal Metastases ◽  
Secondary Tumour ◽  
Osteoblastic Lesions

Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both the formation/development of the associated lesion, and growth of the secondary tumour. Using osteoblasts as a model system, we observed that PCa cells and their conditioned medium could stimulate and increase mineralisation and osteoblasts’ differentiation. Secreted factors within PCa-conditioned medium responsible for osteoblastic changes included small extracellular vesicles (sEVs), which were sufficient to drive osteoblastogenesis. Using MiR-seq, we profiled the miRNA content of PCa sEVs, showing that miR-16-5p was highly ex-pressed. MiR-16 was subsequently higher in EV-treated 7F2 cells and a miR-16 mimic could also stimulate mineralisation. Next, using RNA-seq of extracellular vesicle (EV)-treated 7F2 cells, we observed a large degree of gene downregulation and an increased mineralisation. Ingenuity® Pathway Analysis (IPA®) revealed that miR-16-5p (and other miRs) was a likely upstream effec-tor. MiR-16-5p targets in 7F2 cells, possibly involved in osteoblastogenesis, were included for val-idation, namely AXIN2, PLSCR4, ADRB2 and DLL1. We then confirmed the targeting and dow-regulation of these genes by sEV miR-16-5p using luciferase UTR (untranslated region) reporters. Conversely, the overexpression of PLSCR4, ADRB2 and DLL1 lead to decreased osteoblastogene-sis. These results indicate that miR-16 is an inducer of osteoblastogenesis and is transmitted through prostate cancer-derived sEVs. The mechanism is a likely contributor towards the for-mation of osteoblastic lesions in metastatic PCa.

Sign in / Sign up

Export Citation Format

Share Document