Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 11, November, p. 1277–1282

doi: 10.17219/acem/126051

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Exosome EpCAM promotes the metastasis of glioma by targeting the CD44 signaling molecule on the surface of glioma cells

Quan Gu1,A,B,C,F, Xuelin Chen1,B,C,F, Lin Zhou1,B,C,F, Xianglu Liu1,A,D,E,F

1 Department of Neurosurgery, Fudan University Affiliated Zhongshan Hospital Qingpu Branch, Shanghai, China

Abstract

Background. Glioma, the most common primary tumor in the central nervous system, originates from glial cells and has a poor prognosis.
Objectives. This experimental laboratory study was designed to explore the role of epithelial cell adhesion molecule (EpCAM) in the metastasis of glioma.
Material and Methods. Serum samples were collected from patients with non-metastatic or metastatic glioma (n = 20 per group), and healthy volunteers (n = 8). Exosomes were isolated from the serum and the morphological characteristics were observed under a scanning electron microscope (SEM). The expression of CD81 and CD63 was measured to identify exosomes. Glioma tissue and the adjacent normal tissue samples were obtained from patients with non-metastatic or metastatic glioma (n = 12 per group). Meanwhile, 4 normal brain tissue samples were collected. The expression of CD44, hyaluronan-mediated motility receptor (HMMR), and matrix metalloproteinase-9 (MMP-9) was determined in each group using immunohistochemistry. The protein expression of CD44, HMMR, matrix metalloproteinase-2 (MMP-2), MMP-9, and selectin E (SELE) was measured with western blotting.
Results. Exosomes were present in the serum, and the proteins CD81 and CD63 were expressed in all 3 groups. CD44 was highly expressed in the non-metastasis and metastasis groups. The expression of HMMR and MMP-9 in the Adj-metastasis and Adj-non-metastasis groups was high, while in the other groups, the levels were low. The expression of CD44 in the metastasis and non-metastasis groups was significantly higher than that of the negative control (NC) group, and the expression in the metastasis group was higher than that of the non-metastasis group. The MMP-2 and MMP-9 were not found in either the metastasis or non-metastasis group. The protein expression of HMMR and SELE was high in all groups.
Conclusion. Exosome EpCAM promoted the metastasis of glioma by targeting CD44.

Key words

metastasis, CD44, glioma, exosome, epithelial cell adhesion molecule

References (25)

  1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Eng J Med. 2015;372(26):2499–2508.
  2. Iwadate Y, Matsutani T, Hirono S, Shinozaki N, Saeki N. Transforming growth factor-β and stem cell markers are highly expressed around necrotic areas in glioblastoma. J Neurooncol. 2016;129(1):101–107.
  3. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016;131(6):803–820.
  4. Zeng T, Cui D, Gao L. Glioma: An overview of current classifications, characteristics, molecular biology and target therapies. Front Biosci (Landmark Ed). 2015;20:1104–1115.
  5. Jeon BN, Yoo JY, Choi WI, Lee CE, Yoon HG, Hur MW. Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors. J Biol Chem. 2008;283(48):33199–33210.
  6. Kurtz JE, Dufour P. Adecatumumab: An anti-EpCAM monoclonal antibody, from the bench to the bedside. Exp Opin Biol Ther. 2010;10(6):951–958.
  7. Trzpis M, McLaughlin PMJ, de Leij LMFH, Harmsen MC. Epithelial cell adhesion molecule: More than a carcinoma marker and adhesion molecule. Am J Pathol. 2007;171(2):386–395.
  8. Went PTH, Lugli A, Meier S, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122–128.
  9. Maetzel D, Denzel S, Mack B, et al. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11(2):162–171.
  10. Cimino A, Halushka M, Illei P, Wu X, Sukumar S, Argani P. Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases. Breast Cancer Res Treat. 2010;123(3):701–708.
  11. Du W, Ji H, Cao S, et al. EpCAM: A potential antimetastatic target for gastric cancer (Retraction of vol 55, pg 2165, 2010). Digest Dis Sci. 2013;58(6):1811.
  12. Stoecklein NH, Siegmund A, Scheunemann P, et al. Ep-CAM expression in squamous cell carcinoma of the esophagus: A potential therapeutic target and prognostic marker. BMC Cancer. 2006;6:165.
  13. Hu B, Wang Q, Wang YA, et al. Epigenetic activation of WNT5A drives glioblastoma stem cell differentiation and invasive growth. Cell. 2016;167(5):1281–1295.e18.
  14. Kalluri R. The biology and function of exosomes in cancer. J Clin Invest. 2016;126(4):1208–1215.
  15. Zhao R, Zhang Y, Zhang X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer. 2018;17:68.
  16. Bang C, Thum T. Exosomes: New players in cell–cell communication. Int J Biochem Cell Biol. 2012;44(11):2060–2064.
  17. Sivori S, Falco M, Della Chiesa M, et al. CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: Induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci U S A. 2004;101(27):10116–10121.
  18. Ji H, Greening DW, Barnes TW, et al. Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics. 2013;13(10–11):1672–1686.
  19. Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: A diagnostic marker for lung cancer. Clin Lung Cancer. 2009;10(1):42–46.
  20. Kajita M, Itoh Y, Chiba T, et al. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol. 2001;153(5):893–904.
  21. Senbanjo LT, Chellaiah MA. CD44: A multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front Cell Dev Biol. 2017;5:18.
  22. Wielenga VJM, Heider KH, Johan G, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53(20):4754–4756.
  23. Fu J, Yang Q, Sai K, et al. TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells. Neuro Oncol. 2013;15(10):1353–1365.
  24. Liu W, Ma J, Cheng Y, et al. HMMR antisense RNA 1, a novel long noncoding RNA, regulates the progression of basal-like breast cancer cells. Breast Cancer (Dove Med Press). 2016;8:223–229.
  25. Li J, Ji X, Wang H. Targeting long noncoding RNA HMMR-AS1 suppresses and radiosensitizes glioblastoma. Neoplasia. 2018;20(5):456–466.