scholarly journals Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 591
Author(s):  
Xin-Le Yap ◽  
Bayden Wood ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bey-Hing Goh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Prostate Cancer Screening ◽  
Principal Component ◽  
Urine Samples ◽  
Cancer Type ◽  
Marker Proteins ◽  
Novel Strategy ◽  
Ir Spectroscopic

Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

scholarly journals Study of prostate cancer-derived extracellular vesicles in urine using IR spectroscopy

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Xin-Le Yap ◽  
Teng-Aik Ong ◽  
Jasmine Lim ◽  
Bayden Wood ◽  
Wai-Leng Lee
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Attenuated Total Reflection ◽  
Urine Samples ◽  
Early Screening ◽  
Linear Discriminant ◽  
Non Invasive ◽  
Potential Biomarker

Prostate cancer (PCa) is the third most frequent cancer in men and prostate-specific antigen is currently the biomarker used despite its low specificity. Lately, extracellular vesicles (EVs) which are secreted by all types of cells have raised research interest for their association with cancer progression. Urinary EVs UEVs) has emerged as a potential biomarker for PCa detection as it is non-invasive and urine samples are easily obtained from patients. Therefore, we hypothesize that PCa cells secrete EVs containing a unique set of biomolecules which can be exploited as a signature profile of the cancer. In this study, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy was used for analysis of the UEVs aiming to obtain a signature spectrum for early detection of PCa. Urine samples from PCa and healthy subjects were subjected to ultracentrifugation for isolation of UEVs. Principal Component Analysis (PCA) indicated that FTIR spectra of the UEVs of PCa patients are distinct from those of healthy individuals at the following wavenumber values: amide I peak (1640 cm-1), RNA ribose peak (1120 cm-1), C-C, C-N stretch peak (967 cm-1) and C4–C5/C=N, imidazole ring peak (1610 cm-1). The obtained IR spectra were also analyzed using Linear Discriminant Analysis (LDA) and the resulting diagnostic classifier for PCa achieved a sensitivity of 83.33% and a specificity of 60%. In conclusion, ATR-FTIR analysis of UEVs in combine with PCA-LDA statistic model described in this study may offer a novel strategy for the development of a non-invasive urine test for early screening of prostate 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 miR-26a regulates extracellular vesicle secretion from prostate cancer cells via targeting SHC4, PFDN4 and CHORDC1

2019 ◽  
Author(s):  
Fumihiko Urabe ◽  
Nobuyoshi Kosaka ◽  
Yurika Sawa ◽  
Tomofumi Yamamoto ◽  
Yusuke Yamamoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Suppressive Effect ◽  
Prostate Cancer Cells ◽  
Detailed Mechanism ◽  
Novel Strategy ◽  
Vesicle Secretion

AbstractExtracellular vesicles (EVs) are known to be involved in intercellular communication during cancer progression; thus, elucidating the detailed mechanism will contribute to the development of a novel strategy for EV-targeted cancer treatment. However, the biogenesis of EVs in cancer cells is not completely understood. MicroRNAs (miRNAs) regulate a variety of physiological and pathological phenomena; thus, miRNAs could regulate EV secretion. Here, we performed high-throughput miRNA-based screening to identify the regulators of EV secretion using an ExoScreen assay. By using this miRNA-based screening, we identified miR-26a, which was reported as a tumor suppressive miRNA, as a miRNA involved in EV secretion from prostate cancer (PCa) cells. In addition, we found that the SHC4, PFDN4, and CHORDC1 genes regulate EV secretion in PCa cells. Suppression of these genes by siRNAs significantly inhibited the secretion of EVs in PCa cells. Furthermore, the progression of PCa cells was inhibited in an in vivo study. On the other hand, injection of EVs isolated from PCa cells partially rescued this suppressive effect on tumor growth. Taken together, our findings suggest that miR-26a regulates EV secretion via targeting SHC4, PFDN4, and CHORDC1 in PCa cells, resulting in the suppression of PCa progression.

scholarly journals MP16-18 THE ROLE OF CANCER-ASSOCIATED FIBROBLASTS AND THEIR EXTRACELLULAR VESICLES IN PROSTATE CANCER PROGRESSION

2020 ◽  
Vol 203 ◽  
pp. e222
Author(s):  
Johannes Linxweiler* ◽  
Angela Zaccagnino ◽  
Dirk Himbert ◽  
Turkan Hajili ◽  
Philip Zeuschner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cancer Associated Fibroblasts ◽  
Prostate Cancer Progression

scholarly journals Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles

2019 ◽  
Author(s):  
Javier Mariscal ◽  
Tatyana Vagner ◽  
Minhyung Kim ◽  
Bo Zhou ◽  
Andrew Chin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Large Scale ◽  
Biological Processes ◽  
Label Free ◽  
Disease Biomarkers ◽  
Novel Approach ◽  
Small Cancer ◽  
Promising Source

AbstractExtracellular vesicles (EVs) are membrane-enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L- and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.

scholarly journals The itinerary of circulating miRNAs – implications for cancer progression and diagnosis

2021 ◽  
Vol 90 (2) ◽  
pp. e516
Author(s):  
Przemysław Szałata ◽  
Anna-Maria Guner ◽  
Michalina Raczkowska ◽  
Julia Smyrek ◽  
Dominika Szaj ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Target Cell ◽  
Biological Fluids ◽  
Tumour Microenvironment ◽  
High Density Lipoproteins ◽  
Cancer Type ◽  
Circulating Mirna ◽  
Extracellular Mirna

microRNAs (miRNAs) are non-coding RNAs that regulate gene expression and protect cells from foreign nucleic acids. miRNA is produced in the nucleus and processed in the cytoplasm. These small nucleic acid molecules are released from cells to the extracellular matrix (extracellular miRNA, ex-miRNA) and reach blood plasma (circulating miRNA). Circulating miRNA can also be detected in other biological fluids, such as saliva, cerebrospinal fluid or urine, and it is usually carried by proteins or extracellular vesicles. Argonaute-miRNA, or miRNA-lipoprotein complex, protect miRNA from being degraded. The entrance of extracellular miRNA into a target cell is mediated by endocytosis and membrane fusion of extracellular vesicles. Additionally, miRNA can also be delivered in high-density lipoproteins by means of interactions with scavenger receptors. miRNAs absorbed into a cell can act as tumour promoters (oncomirs), or suppressors by inhibiting the translation process of the target mRNAs, thus, affecting cells in the tumour microenvironment. miRNA can impact other cells by supporting tumour growth, promoting angiogenesis and modulating the immune system. Molecular high-throughput methods are employed to detect circulating miRNA, and a potentially helpful diagnostic test has been designed to characterise the cancer type. In this review, we aim to summarise the itinerary of miRNAs from a source cell to a target cell, as well as to show how this class of small nucleic acids participates in intercellular communication. Finally, we highlight examples of miRNAs usage as potential molecular markers and discuss treatment approaches in clinical trials.

scholarly journals Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study

2020 ◽  
Vol 21 (21) ◽  
pp. 8330
Author(s):  
Michelle Davey ◽  
Sami Benzina ◽  
Marc Savoie ◽  
Guy Breault ◽  
Anirban Ghosh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Extracellular Vesicles ◽  
Prostate Cancer Screening ◽  
Quantitative Polymerase Chain Reaction ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Test Accuracy ◽  
Expression Ratio ◽  
Tissue Biopsy

Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.

Prostate cancer screening using chemometric processing of GC–MS profiles obtained in the headspace above urine samples

2020 ◽  
Vol 1155 ◽  
pp. 122298 ◽  
Author(s):  
Vladislav Deev ◽  
Svetlana Solovieva ◽  
Evgeny Andreev ◽  
Vladimir Protoshchak ◽  
Evgeny Karpushchenko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Screening ◽  
Prostate Cancer Screening ◽  
Urine Samples

scholarly journals Role of Exosomes in Prostate Cancer Metastasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3528
Author(s):  
Theresa Akoto ◽  
Sharanjot Saini
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Cancer Metastasis ◽  
Disseminated Tumor Cells ◽  
Bilayer Membrane ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Metastasis

Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.

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