Exosomal lncRNA‑ATB activates astrocytes that promote glioma cell invasion

  • Authors:
    • Er‑Bao Bian
    • Er‑Feng Chen
    • Ya‑Di Xu
    • Zhi‑Hao Yang
    • Feng Tang
    • Chun‑Chun Ma
    • Hong‑Liang Wang
    • Bing Zhao
  • View Affiliations

  • Published online on: November 23, 2018     https://doi.org/10.3892/ijo.2018.4644
  • Pages: 713-721
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Abstract

Glioma invasion is a main cause of a poor prognosis and relapse in patients suffering from the disease. However, the molecular mechanisms responsible for glioma cell invasion remain poorly understood. In this study, the characteristics of exosomes were identified using electron microscope (TEM), and western blot analysis. The potential mechanism of long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) was demonstrated using luciferase reporter assays and RNA immunoprecipitation. We found that glioma cell‑derived exosomes promoted the activation of astrocytes and had the ability to shuttle long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) to astrocytes. More importantly, lncRNA‑ATB activated astrocytes through the suppression of microRNA (miRNA or miR)‑204‑3p in an Argonaute 2 (Ago2)‑dependent manner. Furthermore, astrocytes activated by lncRNA‑ATB in turn promoted the migration and invasion of glioma cells. Taken together, the findings of this study suggest that lncRNA‑ATB may play an important role in modulating glioma microenvironment through exosomes. Thus, a better understanding of this process may provide implications for the prevention of highly invasive glioma.

References

1 

Johnson DR and O’Neill BP: Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol. 107:359–364. 2012. View Article : Google Scholar

2 

Avril T, Vauleon E, Tanguy-Royer S, Mosser J and Quillien V: Mechanisms of immunomodulation in human glioblastoma. Immunotherapy. 3(Suppl 4): 42–44. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Coniglio SJ and Segall JE: Review: Molecular mechanism of microglia stimulated glioblastoma invasion. Matrix Biol. 32:372–380. 2013. View Article : Google Scholar : PubMed/NCBI

4 

D’Asti E, Garnier D, Lee TH, Montermini L, Meehan B and Rak J: Oncogenic extracellular vesicles in brain tumor progression. Front Physiol. 3:2942012. View Article : Google Scholar :

5 

Fidler IJ, Balasubramanian K, Lin Q, Kim SW and Kim SJ: The brain microenvironment and cancer metastasis. Mol Cells. 30:93–98. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Katz AM, Amankulor NM, Pitter K, Helmy K, Squatrito M and Holland EC: Astrocyte-specific expression patterns associated with the PDGF-induced glioma microenvironment. PLoS One. 7:e324532012. View Article : Google Scholar : PubMed/NCBI

7 

Lee J, Borboa AK, Baird A and Eliceiri BP: Non-invasive quantification of brain tumor-induced astrogliosis. BMC Neurosci. 12:92011. View Article : Google Scholar : PubMed/NCBI

8 

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

9 

Τhéry C: Exosomes: Secreted vesicles and intercellular communications. F1000 Biol Rep. 3:152011. View Article : Google Scholar : PubMed/NCBI

10 

Batrakova EV and Kim MS: Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 219:396–405. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Aalberts M, van Dissel-Emiliani FM, van Adrichem NP, van Wijnen M, Wauben MH, Stout TA and Stoorvogel W: Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol Reprod. 86:822012. View Article : Google Scholar

12 

Friand V, David G and Zimmermann P: Syntenin and syndecan in the biogenesis of exosomes. Biol Cell. 107:331–341. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Hagiwara K, Ochiya T and Kosaka N: A paradigm shift for extracellular vesicles as small RNA carriers: From cellular waste elimination to therapeutic applications. Drug Deliv Transl Res. 4:31–37. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Khalyfa A and Gozal D: Exosomal miRNAs as potential biomarkers of cardiovascular risk in children. J Transl Med. 12:1622014. View Article : Google Scholar : PubMed/NCBI

15 

Madison MN and Okeoma CM: Exosomes: Implications in HIV-1 Pathogenesis. Viruses. 7:4093–4118. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Hirsch E, Hilfiker-Kleiner D, Balligand JL, Tarone G, De Windt L, Bauersachs J, Ferdinandy P, Davidson S, Hausenloy DJ and Schulz R: Interaction of the heart and its close and distant neighbours: Report of the Meeting of the ESC Working Groups Myocardial Function and Cellular Biology. Cardiovasc Res. 99:595–599. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Lugini L, Cecchetti S, Huber V, Luciani F, Macchia G, Spadaro F, Paris L, Abalsamo L, Colone M, Molinari A, et al: Immune surveillance properties of human NK cell-derived exosomes. J Immunol. 189:2833–2842. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Zhu H and Fan GC: Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am J Cardiovasc Dis. 1:138–149. 2011.PubMed/NCBI

19 

Madison MN, Jones PH and Okeoma CM: Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex. Virology. 482:189–201. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Vojtech L, Woo S, Hughes S, Levy C, Ballweber L, Sauteraud RP, Strobl J, Westerberg K, Gottardo R, Tewari M, et al: Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res. 42:7290–7304. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Clayton A: Cancer cells use exosomes as tools to manipulate immunity and the microenvironment. OncoImmunology. 1:78–80. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Epple LM, Griffiths SG, Dechkovskaia AM, Dusto NL, White J, Ouellette RJ, Anchordoquy TJ, Bemis LT and Graner MW: Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. PLoS One. 7:e420642012. View Article : Google Scholar : PubMed/NCBI

23 

Taylor DD and Gercel-Taylor C: Exosomes/microvesicles: Mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol. 33:441–454. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, et al: A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepato-cellular carcinoma. Cancer Cell. 25:666–681. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Ma CC, Xiong Z, Zhu GN, Wang C, Zong G, Wang HL, Bian EB and Zhao B: Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a. J Exp Clin Cancer Res. 35:902016. View Article : Google Scholar : PubMed/NCBI

26 

Ma J, Cui X, Rong Y, Zhou Y, Guo Y, Zhou M, Xiao L and Chen W: Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers’ Pneumoconiosis: A Case-Control Study. Int J Mol Sci. 17:172016. View Article : Google Scholar

27 

Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, Yu Y, Chow A, O’Connor ST, Chin AR, et al: Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 25:501–515. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

29 

van der Vos KE, Abels ER, Zhang X, Lai C, Carrizosa E, Oakley D, Prabhakar S, Mardini O, Crommentuijn MH, Skog J, et al: Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neurooncol. 18:58–69. 2016.

30 

Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, et al: Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 26:707–721. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Clayton A, Mitchell JP, Court J, Mason MD and Tabi Z: Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 67:7458–7466. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J and Ratajczak MZ: Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 113:752–760. 2005. View Article : Google Scholar

33 

EL Andaloussi S, Mäger I, Breakefield XO and Wood MJ: Extracellular vesicles: Biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 12:347–357. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Milane L, Singh A, Mattheolabakis G, Suresh M and Amiji MM: Exosome mediated communication within the tumor microenvironment. J Control Release. 219:278–294. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringnér M, Mörgelin M, Bourseau-Guilmain E, Bengzon J and Belting M: Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci USA. 110:7312–7317. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Svensson KJ, Kucharzewska P, Christianson HC, Sköld S, Löfstedt T, Johansson MC, Mörgelin M, Bengzon J, Ruf W and Belting M: Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc Natl Acad Sci USA. 108:13147–13152. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Qu L, Ding J, Chen C, Wu ZJ, Liu B, Gao Y, Chen W, Liu F, Sun W, Li XF, et al: Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Cancer Cell. 29:653–668. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Grosche J, Matyash V, Möller T, Verkhratsky A, Reichenbach A and Kettenmann H: Microdomains for neuron-glia interaction: Parallel fiber signaling to Bergmann glial cells. Nat Neurosci. 2:139–143. 1999. View Article : Google Scholar : PubMed/NCBI

39 

Gagliano N, Costa F, Cossetti C, Pettinari L, Bassi R, Chiriva-Internati M, Cobos E, Gioia M and Pluchino S: Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model. Oncol Rep. 22:1349–1356. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Fitzgerald DP, Palmieri D, Hua E, Hargrave E, Herring JM, Qian Y, Vega-Valle E, Weil RJ, Stark AM, Vortmeyer AO, et al: Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis. 25:799–810. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Seike T, Fujita K, Yamakawa Y, Kido MA, Takiguchi S, Teramoto N, Iguchi H and Noda M: Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin Exp Metastasis. 28:13–25. 2011. View Article : Google Scholar :

42 

Barbero S, Bajetto A, Bonavia R, Porcile C, Piccioli P, Pirani P, Ravetti JL, Zona G, Spaziante R, Florio T, et al: Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro. Ann N Y Acad Sci. 973:60–69. 2002. View Article : Google Scholar : PubMed/NCBI

43 

Biasoli D, Sobrinho MF, da Fonseca AC, de Matos DG, Romão L, de Moraes Maciel R, Rehen SK, Moura-Neto V, Borges HL and Lima FR: Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy. Oncogenesis. 3:e1232014. View Article : Google Scholar : PubMed/NCBI

44 

Chen W, Xia T, Wang D, Huang B, Zhao P, Wang J, Qu X and Li X: Human astrocytes secrete IL-6 to promote glioma migration and invasion through upregulation of cytomembrane MMP14. Oncotarget. 7:62425–62438. 2016.PubMed/NCBI

45 

Lei K, Liang X, Gao Y, Xu B, Xu Y, Li Y, Tao Y, Shi W and Liu J: Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFβ2 feedback loop. Biochem Biophys Res Commun. 484:514–521. 2017. View Article : Google Scholar : PubMed/NCBI

46 

Zhu HY, Bai WD, Li C, Zheng Z, Guan H, Liu JQ, Yang XK, Han SC, Gao JX, Wang HT, et al: Knockdown of lncRNA-ATB suppresses autocrine secretion of TGF-β2 by targeting ZNF217 via miR-200c in keloid fibroblasts. Sci Rep. 6:247282016. View Article : Google Scholar

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APA
Bian, E., Chen, E., Xu, Y., Yang, Z., Tang, F., Ma, C. ... Zhao, B. (2019). Exosomal lncRNA‑ATB activates astrocytes that promote glioma cell invasion. International Journal of Oncology, 54, 713-721. https://doi.org/10.3892/ijo.2018.4644
MLA
Bian, E., Chen, E., Xu, Y., Yang, Z., Tang, F., Ma, C., Wang, H., Zhao, B."Exosomal lncRNA‑ATB activates astrocytes that promote glioma cell invasion". International Journal of Oncology 54.2 (2019): 713-721.
Chicago
Bian, E., Chen, E., Xu, Y., Yang, Z., Tang, F., Ma, C., Wang, H., Zhao, B."Exosomal lncRNA‑ATB activates astrocytes that promote glioma cell invasion". International Journal of Oncology 54, no. 2 (2019): 713-721. https://doi.org/10.3892/ijo.2018.4644