Distinct Prostate Cancer-related MRNA Cargo in Extracellular Vesicle Subsets from Prostate Cell Lines

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2017 Feb 2

PMID 28143451

Citations 38

Authors

Elisa Lazaro-Ibanez

Taral R Lunavat

Su Chul Jang

Carmen Escobedo-Lucea

Jorge Oliver-De La Cruz

Pia Siljander

Jan Lotvall

Marjo Yliperttula

Affiliations

Soon will be listed here.

Abstract

Background: Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed.

Methods: We isolated MVs and EXOs from PC-3 and LNCaP prostate cancer cells by differential centrifugation and compared them to EVs derived from the benign PNT2 prostate cells. The relative mRNA levels of 84 prostate cancer-related genes were investigated and validated using quantitative reverse transcription PCR arrays.

Results: Based on the mRNA abundance, MVs rather than EXOs were enriched in the analyzed transcripts, providing a snapshot of the tumor transcriptome. LNCaP MVs specifically contained significantly increased mRNA levels of NK3 Homeobox 1 (NKX3-1), transmembrane protease serine 2 (TMPRSS2), and tumor protein 53 (TP53) genes, whereas PC-3 MVs carried increased mRNA levels of several genes including, caveolin-2 (CAV2), glutathione S-transferase pi 1 (GSTP1), pescadillo ribosomal biogenesis factor 1 (PES1), calmodulin regulated spectrin associated protein 1 (CAMSAP1), zinc-finger protein 185 (ZNF185), and others compared to PNT2 MVs. Additionally, ETS variant 1 (ETV1) and fatty acid synthase (FASN) mRNAs identified in LNCaP- and PC-3- derived MVs highly correlated with prostate cancer progression.

Conclusions: Our study provides new understandings of the variability of the mRNA cargo of MVs and EXOs from different cell lines despite same cancer origin, which is essential to better understand the the proportion of the cell transcriptome that can be detected within EVs and to evaluate their role in disease diagnosis.

Citing Articles

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References

Nakamura Y, Felizola S, Kurotaki Y, Fujishima F, McNamara K, Suzuki T . Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer. Prostate. 2012; 73(6):590-5. DOI: 10.1002/pros.22599. View

Henrique R, Costa V, Cerveira N, Carvalho A, Hoque M, Ribeiro F . Hypermethylation of Cyclin D2 is associated with loss of mRNA expression and tumor development in prostate cancer. J Mol Med (Berl). 2006; 84(11):911-8. DOI: 10.1007/s00109-006-0099-4. View

Jenjaroenpun P, Kremenska Y, Nair V, Kremenskoy M, Joseph B, Kurochkin I . Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing. PeerJ. 2013; 1:e201. PMC: 3828613. DOI: 10.7717/peerj.201. View

LeBeau A, Kostova M, Craik C, Denmeade S . Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer. Biol Chem. 2010; 391(4):333-43. PMC: 3454521. DOI: 10.1515/BC.2010.044. View

Ekstrom K, Valadi H, Sjostrand M, Malmhall C, Bossios A, Eldh M . Characterization of mRNA and microRNA in human mast cell-derived exosomes and their transfer to other mast cells and blood CD34 progenitor cells. J Extracell Vesicles. 2013; 1. PMC: 3760639. DOI: 10.3402/jev.v1i0.18389. View

Huang M, Koizumi A, Narita S, Inoue T, Tsuchiya N, Nakanishi H . Diet-induced alteration of fatty acid synthase in prostate cancer progression. Oncogenesis. 2016; 5:e195. PMC: 5154344. DOI: 10.1038/oncsis.2015.42. View

Kanada M, Bachmann M, Hardy J, Frimannson D, Bronsart L, Wang A . Differential fates of biomolecules delivered to target cells via extracellular vesicles. Proc Natl Acad Sci U S A. 2015; 112(12):E1433-42. PMC: 4378439. DOI: 10.1073/pnas.1418401112. View

Shen M, Abate-Shen C . Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010; 24(18):1967-2000. PMC: 2939361. DOI: 10.1101/gad.1965810. View

Sillars-Hardebol A, Carvalho B, Belien J, de Wit M, Delis-van Diemen P, Tijssen M . CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression. Cell Oncol (Dordr). 2012; 35(4):293-300. DOI: 10.1007/s13402-012-0088-2. View

10.

Sugie S, Mukai S, Yamasaki K, Kamibeppu T, Tsukino H, Kamoto T . Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression. Cancer Genomics Proteomics. 2015; 12(6):391-6. View

11.

Pigati L, Yaddanapudi S, Iyengar R, Kim D, Hearn S, Danforth D . Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010; 5(10):e13515. PMC: 2958125. DOI: 10.1371/journal.pone.0013515. View

12.

Meiers I, Shanks J, Bostwick D . Glutathione S-transferase pi (GSTP1) hypermethylation in prostate cancer: review 2007. Pathology. 2007; 39(3):299-304. DOI: 10.1080/00313020701329906. View

13.

Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee J, Lotvall J . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9(6):654-9. DOI: 10.1038/ncb1596. View

14.

Raposo G, Stoorvogel W . Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013; 200(4):373-83. PMC: 3575529. DOI: 10.1083/jcb.201211138. View

15.

Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P . Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006; 20(5):847-56. DOI: 10.1038/sj.leu.2404132. View

16.

Thery C, Amigorena S, Raposo G, Clayton A . Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2008; Chapter 3:Unit 3.22. DOI: 10.1002/0471143030.cb0322s30. View

17.

Enderle D, Spiel A, Coticchia C, Berghoff E, Mueller R, Schlumpberger M . Characterization of RNA from Exosomes and Other Extracellular Vesicles Isolated by a Novel Spin Column-Based Method. PLoS One. 2015; 10(8):e0136133. PMC: 4552735. DOI: 10.1371/journal.pone.0136133. View

18.

Yanez-Mo M, Siljander P, Andreu Z, Bedina Zavec A, Borras F, Buzas E . Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015; 4:27066. PMC: 4433489. DOI: 10.3402/jev.v4.27066. View

19.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

20.

Minciacchi V, You S, Spinelli C, Morley S, Zandian M, Aspuria P . Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles. Oncotarget. 2015; 6(13):11327-41. PMC: 4484459. DOI: 10.18632/oncotarget.3598. View