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22.11.2018 | Original Article

Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells

verfasst von: Yusuke Matsuura, Hiroshi Wada, Hidetoshi Eguchi, Kunihito Gotoh, Shogo Kobayashi, Mitsuru Kinoshita, Masahiko Kubo, Koji Hayashi, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Koichi Kawamoto, Yutaka Takeda, Masahiro Tanemura, Koji Umeshita, Yuichiro Doki, Masaki Mori

Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2019

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Abstract

Purpose

In this study, we aim to clarify whether exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia affect angiogenesis in endothelial cells.

Methods

Exosomes derived from human liver cancer cell lines were cultured under hypoxic or normoxic conditions for 24 h, isolated using ExoQuick-TC^®, and co-cultured with HUVECs to evaluate angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC.

Results

Exosomes under hypoxia remarkably enhanced tube formation of HUVECs. Both cellular and exosomal miR-155 were significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia in HUVECs, and high expression of exosomal miR-155 in preoperative plasma was significantly correlated with early recurrence.

Conclusion

These results suggest that exosomes derived from HCC cells under hypoxia induce tube formation of HUVECs and that exosomal miR-155 may affect angiogenic activity in HCC.

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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed

Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917.CrossRefPubMed

Tomimaru Y, Wada H, Eguchi H, et al. Clinical significance of surgical resection of metastatic lymph nodes from hepatocellular carcinoma. Surg Today. 2015;45:1112–1120.CrossRefPubMed

Hammad A, Kaido A, Ogawa K, et al. Liver transplantation for advanced hepatocellular carcinoma in patients with Child-Pugh A and B. Surg Today. 2016;46:248–254.CrossRefPubMed

Lo CM, Ngan H, Tso WK, et al. Randomizes controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171.CrossRefPubMed

Liou TC, Shih SC, Kao CR, Chou SY, Lin SC, Wang HY. Pulmonary metastasis of hepatocellular carcinoma associated with transarterial chemoembolization. J Hepatol. 1995;23:563–568.CrossRefPubMed

Liu L, Ren ZG, Shen Y, et al. Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: relevance of epithelial-mesenchymal transition. Cancer Sci. 2010;101:120–128.CrossRefPubMed

Vaupel P. Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. Oncologist. 2008;13:21–26.CrossRefPubMed

Bennewith KL, Dedhar S. Targeting hypoxic tumor cells to overcome metastasis. BMC Cancer. 2011;11:504.CrossRefPubMedPubMedCentral

10.

Park JE, Tan HS, Datta A, et al. Hypoxic tumor cell modulates its microenvironment enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteom. 2010;9:1085–1099.CrossRef

11.

Simpson RJ, Lim JW, Moritz RL, Mathivanan S. Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteom. 2009;6:267–283.CrossRef

12.

Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumor growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470-06.CrossRef

13.

Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene. 2013;32:2747–2755.CrossRefPubMed

14.

Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional nephrilysin-bound exosomes. Sci Rep. 2013;3:1197.CrossRefPubMedPubMedCentral

15.

Yang MH, Chen CL, Chau GY, et al. Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology. 2009;50:1464–1474.CrossRefPubMed

16.

Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285:17442–17452.CrossRefPubMedPubMedCentral

17.

Schmittgen TD, Jiang J, Liu Q, Yang L. A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 2004;32:e43.CrossRefPubMedPubMedCentral

18.

Eguchi H, Nagano H, Yamamoto H, et al. Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells. Clin Cancer Res. 2000;6:2881–2890.PubMed

19.

Iwagami Y, Eguchi H, Nagano H, et al. miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1. Br J Cancer. 2013;109:502–511.CrossRefPubMedPubMedCentral

20.

Wada H, Nagano H, Yamamoto H, et al. Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1α. Liver Int. 2006;26:414–423.CrossRefPubMed

21.

Huang CS, Yu W, Cui H, et al. Increased expression of miR-21 predicts poor prognosis in patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8:7234–7238.PubMedPubMedCentral

22.

Yang X, Zhang XF, Lu X, et al. MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway. Hepatology. 2014;59:1874–1885.CrossRefPubMed

23.

Xu Q, Zhang M, Tu J, Pang L, Cai W, Liu X. MicroRNA-122 affects cell aggressiveness and apoptosis by targeting PKM2 in human hepatocellular carcinoma. Oncol Rep. 2015;34:2054–2064.CrossRefPubMed

24.

Zhu K, Pan Q, Zhang X, et al. MiR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression. Carcinogenesis. 2013;34:2071–2079.CrossRefPubMed

25.

Guan C, Yang F, He X, et al. Clinical significance of microRNA-155 expression in hepatocellular carcinoma. Oncol Lett. 2016;11:1574–1580.CrossRefPubMed

26.

Zhang L, Wang W, Li X, et al. MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2. Int J Oncol. 2016;48:2425–2434.CrossRefPubMed

27.

Chen L, Chu F, Cao Y, Shao J, Wang F. Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma. Tumor Biol. 2015;36:7439–7447.CrossRef

28.

Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 1820;940–8:2012.

29.

Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med. 2013;91:431–437.CrossRefPubMed

30.

Wang Z, Chen JQ, Liu JL, Tian L. Exosomes in tumor microenvironment: novel transporters and biomarkers. J Transl Med. 2016;14:297.CrossRefPubMedPubMedCentral

31.

Fais S, Logozzi M, Lugini L, et al. Exosomes: the ideal nanovectors for biodelivery. Biol Chem. 2013;394:1–15.CrossRefPubMed

32.

King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer. 2012;12:421.CrossRefPubMedPubMedCentral

33.

Kogure T, Lin WL, Yan IK, Braconi C, Patel T. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology. 2011;54:1237–1248.CrossRefPubMed

34.

Qu JL, Qu XJ, Zhao MF, et al. Gastric cancer exosomes promote tumor cell proliferation through PI3K?Akt and MAPK/ERK activation. Dig Liver Dis. 2009;41:875–880.CrossRefPubMed

35.

Tadokoro H, Umezu T, Ohyashiki K, Hirano T, Ohyashiki JH. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J Biol Chem. 2013;288:34343–34351.CrossRefPubMedPubMedCentral

36.

Toiyama Y, Tanala K, Inoue Y, Mohri Y, Kusunoki M. Circulating cell-free microRNAs as biomarkers for colorectal cancers. Surg Today. 2016;46:13–24.CrossRefPubMed

37.

Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.CrossRefPubMed

38.

Jiang S, Zhang HW, Lu MH, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokines signaling 1 gene. Cancer Res. 2010;70:3119–3127.CrossRefPubMed

39.

Kong W, Yang H, He L, et al. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008;28:6773–6784.CrossRefPubMedPubMedCentral

40.

O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 2007;104:1604–1609.CrossRefPubMedPubMedCentral

41.

Kong W, He L, Richards EJ, et al. Upregulation of miRNA-155 promotes tumor angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene. 2014;33:679–689.CrossRefPubMed

42.

Bruning U, Cerone L, Neufeld Z, et al. MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol. 2011;19:4087–4096.CrossRef

43.

Robertson ED, Wasylyk C, Ye T, Jung AC, Wasylyk B. The oncogenic MicroRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response. PLoS ONE. 2014;9:e113050.CrossRefPubMedPubMedCentral

44.

Liu Q, Yu Z, Yuan S, et al. Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget. 2017;8:13048–13058.PubMed

Titel: Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells
verfasst von: Yusuke Matsuura
Hiroshi Wada
Hidetoshi Eguchi
Kunihito Gotoh
Shogo Kobayashi
Mitsuru Kinoshita
Masahiko Kubo
Koji Hayashi
Yoshifumi Iwagami
Daisaku Yamada
Tadafumi Asaoka
Takehiro Noda
Koichi Kawamoto
Yutaka Takeda
Masahiro Tanemura
Koji Umeshita
Yuichiro Doki
Masaki Mori
Publikationsdatum: 22.11.2018
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 3/2019
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-018-5380-1

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Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

Purpose

Methods

Results

Conclusion

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