Lung cancer exosomes initiate global long non-coding RNA changes in mesenchymal stem cells

Wang,Shihua; Li,Xiaoxia; Zhu,Rongjia; Han,Qin; Zhao,Robert Chunhua

doi:10.3892/ijo.2015.3272

Lung cancer exosomes initiate global long non-coding RNA changes in mesenchymal stem cells

Authors:
- Shihua Wang
- Xiaoxia Li
- Rongjia Zhu
- Qin Han
- Robert Chunhua Zhao
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Affiliations: Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing 100005, P.R. China
Published online on: November 27, 2015 https://doi.org/10.3892/ijo.2015.3272
Pages: 681-689

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Abstract

Mesenchymal stem cells (MSCs) can be attracted to tumor sites and become an important component of the tumor microenvironment, thus contributing to tumor development. Emerging evidence suggests that tumor cells could transfer genetic information into MSCs through the release of exosomes. However, the molecular mechanisms by which tumor exosomes contribute to interactions between MSCs and tumor cells remain largely unknown. In this study, we found that lung tumor cell derived exosomes could inhibit MSCs osteogenic and adipogenic differentiation. We then investigated the involvement of long non-coding RNAs, a new class of regulators, in tumor exosome treated MSCs by a comprehensive lncRNA and mRNA profiling. lncRNAs (9.1%) (2775 out of 30586) and 9.3% of protein-coding mRNA (2439 out of 26109) were differentially expressed (fold-change ≥2; P-value ≤0.05) in lung tumor cell exosome treated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Noteworthy, GO analysis of biological process showed that upregulated mRNAs were enriched in mRNA metabolic process, while downregulated ones were enriched in detection of mechanical stimulus involved in sensory perception. Pathway analysis indicated that 32 pathways were upregulated while 7 were downregulated in A549 exosome treated MSCs. Here, we are the first to determine genome-wide lncRNA expression patterns in exosome treated MSCs by microarray and the results will bring new insights into the mechanisms underlying interactions between tumor cells exosomes and its environmental component the MSCs.

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1	Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, Diprete B, Betz KS, et al: Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 19:257–272. 2011. View Article : Google Scholar : PubMed/NCBI
2	Joyce JA and Pollard JW: Microenvironmental regulation of metastasis. Nat Rev Cancer. 9:239–252. 2009. View Article : Google Scholar : PubMed/NCBI
3	Bhowmick NA and Moses HL: Tumor-stroma interactions. Curr Opin Genet Dev. 15:97–101. 2005. View Article : Google Scholar : PubMed/NCBI
4	Pietras K and Ostman A: Hallmarks of cancer: Interactions with the tumor stroma. Exp Cell Res. 316:1324–1331. 2010. View Article : Google Scholar : PubMed/NCBI
5	Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C and Chen Y: Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 80:267–274. 2006. View Article : Google Scholar
6	Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R and Weinberg RA: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449:557–563. 2007. View Article : Google Scholar : PubMed/NCBI
7	Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI
8	Roorda BD, ter Elst A, Kamps WA and de Bont ES: Bone marrow-derived cells and tumor growth: Contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol. 69:187–198. 2009. View Article : Google Scholar
9	Ye J, Wu D, Wu P, Chen Z and Huang J: The cancer stem cell niche: Cross talk between cancer stem cells and their microenvironment. Tumour Biol. 35:3945–3951. 2014. View Article : Google Scholar : PubMed/NCBI
10	Egeblad M, Nakasone ES and Werb Z: Tumors as organs: Complex tissues that interface with the entire organism. Dev Cell. 18:884–901. 2010. View Article : Google Scholar : PubMed/NCBI
11	Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, Tetta C, Bussolati B and Camussi G: Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 71:5346–5356. 2011. View Article : Google Scholar : PubMed/NCBI
12	Chen WX, Cai YQ, Lv MM, Chen L, Zhong SL, Ma TF, Zhao JH and Tang JH: Exosomes from docetaxel-resistant breast cancer cells alter chemosensitivity by delivering microRNAs. Tumour Biol. 35:9649–9659. 2014. View Article : Google Scholar : PubMed/NCBI
13	Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S and Rivoltini L: Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ. 15:80–88. 2008. View Article : Google Scholar
14	Chowdhury R, Webber JP, Gurney M, Mason MD, Tabi Z and Clayton A: Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget. 6:715–731. 2015. View Article : Google Scholar : PubMed/NCBI
15	Haga H, Yan IK, Takahashi K, Wood J, Zubair A and Patel T: Tumour cell-derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth. J Extracell Vesicles. 4:249002015. View Article : Google Scholar : PubMed/NCBI
16	Yang Y, Bucan V, Baehre H, von der Ohe J, Otte A and Hass R: Acquisition of new tumor cell properties by MSC-derived exosomes. Int J Oncol. 47:244–252. 2015.PubMed/NCBI
17	Cao Y, Sun Z, Liao L, Meng Y, Han Q and Zhao RC: Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun. 332:370–379. 2005. View Article : Google Scholar : PubMed/NCBI
18	Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, Muramatsu K, Fukuda Y, Ogura S, Yamaguchi K, et al: Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One. 5:e132472010. View Article : Google Scholar : PubMed/NCBI
19	Hood JL, Pan H, Lanza GM and Wickline SA: Consortium for Translational Research in Advanced Imaging and Nanomedicine (C-TRAIN): Paracrine induction of endothelium by tumor exosomes. Lab Invest. 89:1317–1328. 2009. View Article : Google Scholar : PubMed/NCBI
20	Boelens MC, Wu TJ, Nabet BY, Xu B, Qiu Y, Yoon T, Azzam DJ, Twyman-Saint Victor C, Wiemann BZ, Ishwaran H, et al: Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 159:499–513. 2014. View Article : Google Scholar : PubMed/NCBI
21	Zhang X, Yuan X, Shi H, Wu L, Qian H and Xu W: Exosomes in cancer: Small particle, big player. J Hematol Oncol. 8:832015. View Article : Google Scholar : PubMed/NCBI
22	Tang MK and Wong AS: Exosomes: Emerging biomarkers and targets for ovarian cancer. Cancer Lett. 367:26–33. 2015. View Article : Google Scholar : PubMed/NCBI
23	Cho JA, Yeo DJ, Son HY, Kim HW, Jung DS, Ko JK, Koh JS, Kim YN and Kim CW: Exosomes: A new delivery system for tumor antigens in cancer immunotherapy. Int J Cancer. 114:613–622. 2005. View Article : Google Scholar
24	Chow A, Zhou W, Liu L, Fong MY, Champer J, Van Haute D, Chin AR, Ren X, Gugiu BG, Meng Z, et al: Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB. Sci Rep. 4:57502014. View Article : Google Scholar
25	Xiao X, Yu S, Li S, Wu J, Ma R, Cao H, Zhu Y and Feng J: Exosomes: Decreased sensitivity of lung cancer A549 cells to cisplatin. PLoS One. 9:e895342014. View Article : Google Scholar : PubMed/NCBI
26	Ohno S, Tachibana M, Fujii T, Ueda S, Kubota H and Nagasue N: Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma. Int J Cancer. 97:770–774. 2002. View Article : Google Scholar : PubMed/NCBI
27	Keleg S, Büchler P, Ludwig R, Büchler MW and Friess H: Invasion and metastasis in pancreatic cancer. Mol Cancer. 2:142003. View Article : Google Scholar : PubMed/NCBI