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Article

YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line

  • Authors:
    • Yasuto Akiyama
    • Tadashi Ashizawa
    • Masaru Komiyama
    • Haruo Miyata
    • Chie Oshita
    • Maho Omiya
    • Akira Iizuka
    • Akiko Kume
    • Takashi Sugino
    • Nakamasa Hayashi
    • Koichi Mitsuya
    • Yoko Nakasu
    • Ken Yamaguchi
  • View Affiliations / Copyright

    Affiliations: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan, Division of Pathology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan, Division of Neurosurgery, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan
  • Pages: 159-166
    |
    Published online on: May 16, 2014
       https://doi.org/10.3892/or.2014.3195
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Abstract

The frequent recurrence of glioblastoma multiforme (GBM) after standard treatment with temozolomide (TMZ) is a crucial issue to be solved in the clinical field. O6‑methylguanine‑DNA methyltransferase (MGMT) is considered one of the major mechanisms involved in TMZ resistance. However, some important mechanisms for TMZ resistance other than MGMT have recently been identified. In the present study, we established a TMZ-resistant (TMZ-R) U87 glioblastoma cell line in vitro and in vivo and investigated novel targeting molecules other than MGMT in those cells. The TMZ-R U87 glioblastoma cell line was established in vitro and in vivo. TMZ-R U87 cells showed a more invasive activity and a shorter survival time in vivo. Gene expression analysis using DNA microarray and quantitative PCR (qPCR) demonstrated that YKL‑40, MAGEC1 and MGMT mRNA expression was upregulated 100-, 83- and 6-fold, respectively in the TMZ-R U87 cell line. Western blot analysis and qPCR demonstrated that STAT3 phosphorylation, STAT3 target genes and stem cell and mesenchymal marker genes were upregulated to a greater extent in the TMZ‑resistant cell line. Notably, short hairpin (sh)RNA‑based inhibition against the YKL‑40 gene resulted in moderate growth inhibition in the resistant cells in vitro and in vivo. Additionally, YKL‑40 gene inhibition exhibited significant suppression of the invasive activity and particularly partially restored the sensitivity to TMZ. Therefore, YKL‑40 may be a novel key molecule in addition to MGMT, that is responsible for TMZ resistance in glioblastoma cell lines and could be a new target to overcome TMZ resistance in recurrent glioblastomas in the future.
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1 

Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Mirimanoff RO, Gorlia T, Mason W, et al: Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol. 24:2563–2569. 2006. View Article : Google Scholar

3 

Trivedi RN, Almeida KH, Fornsaglio JL, Schamus S and Sobol RW: The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death. Cancer Res. 65:6394–6400. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Hegi ME, Diserens AC, Gorlia T, et al: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 352:997–1003. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Quinn JA, Desjardins A, Weingart J, et al: Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 23:7178–7187. 2005.PubMed/NCBI

6 

Quinn JA, Jiang SX, Reardon DA, et al: Phase II trial of temozolomide plus O6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol. 27:1262–1267. 2009.PubMed/NCBI

7 

Murat A, Migliavacca E, Gorlia T, et al: Stem cell-related ‘self-renewal’ signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 26:3015–3024. 2008.

8 

Hunter C, Smith R, Cahill DP, et al: A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res. 66:3987–3991. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Sun S, Lee D, Ho AS, et al: Inhibition of prolyl 4-hydroxylase, beta polypeptide (P4HB) attenuates temozolomide resistance in malignant glioma via the endoplasmic reticulum stress response (ERSR) pathways. Neuro Oncol. 15:562–577. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Mukherjee B, McEllin B, Camacho CV, et al: EGFRvIII and DNA double-strand break repair: a molecular mechanism for radioresistance in glioblastoma. Cancer Res. 69:4252–4259. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Kitange GJ, Carlson BL, Schroeder MA, et al: Expression of CD74 in high grade gliomas: a potential role in temozolomide resistance. J Neurooncol. 100:177–186. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Vlachostergios PJ, Hatzidaki E, Befani CD, Liakos P and Papandreou CN: Bortezomib overcomes MGMT-related resistance of glioblastoma cell lines to temozolomide in a schedule-dependent manner. Invest New Drugs. 31:1169–1181. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kanzawa T, Germano IM, Kondo Y, Ito H, Kyo S and Kondo S: Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide. Br J Cancer. 89:922–929. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Zheng M, Bocangel D, Ramesh R, et al: Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells. Mol Cancer Ther. 7:3842–3851. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Jiang G, Wei ZP, Pei DS, Xin Y, Liu YQ and Zheng JN: A novel approach to overcome temozolomide resistance in glioma and melanoma: Inactivation of MGMT by gene therapy. Biochem Biophys Res Commun. 406:311–314. 2011. View Article : Google Scholar

16 

Tso CL, Shintaku P, Chen J, et al: Primary glioblastomas express mesenchymal stem-like properties. Mol Cancer Res. 4:607–619. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Phillips HS, Kharbanda S, Chen R, et al: Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 9:157–173. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Carro MS, Lim WK, Alvarez MJ, et al: The transcriptional network for mesenchymal transformation of brain tumors. Nature. 463:318–325. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Verhaak RG, Hoadley KA, Purdom E, et al: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 17:98–110. 2010. View Article : Google Scholar

20 

Ashizawa T, Miyata H, Iizuka A, et al: Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma. Int J Oncol. 43:219–227. 2013.PubMed/NCBI

21 

Ashizawa T, Miyata H, Ishii H, et al: Antitumor activity of a novel small molecule STAT3 inhibitor against a human lymphoma cell line with high STAT3 activation. Int J Oncol. 38:1245–1252. 2011.PubMed/NCBI

22 

Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double A, Everitt J, Farningham DAH, Glennie MJ, Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S, Wedge SR and Eccles SA: An ad hoc committee of the National Cancer Research Institute: Guidelines for the welfare and use of animals in cancer research. Br J Cancer. 102:1555–1577. 2010. View Article : Google Scholar

23 

Kohsaka S, Wang L, Yachi K, et al: STAT3 inhibition overcomes temozolomide resistance in glioblastoma by downregulating MGMT expression. Mol Cancer Ther. 11:1289–1299. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI and Kordula T: A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40. J Biol Chem. 286:39893–39903. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Kzhyshkowska J, Gratchev A and Goerdt S: Human chitinases and chitinase-like ptoteins as indicators for inflammation and cancer. Biomark Insights. 3:128–146. 2007.PubMed/NCBI

26 

Shao R, Hamel K, Petersen L, et al: YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene. 28:4456–4468. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Francescone RA, Scully S, Faibish M, et al: Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J Biol Chem. 286:15332–15343. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Tanwar MK, Gilbert MR and Holland EC: Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res. 62:4364–4368. 2002.

29 

Høgdall EV, Johansen JS, Kjaer SK, et al: High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival. Oncol Rep. 10:1535–1538. 2003.PubMed/NCBI

30 

Hormigo A, Gu B, Karimi S, et al: YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res. 12:5698–5704. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Thöm I, Andritzky B, Schuch G, et al: Elevated pretreatment serum concentration of YKL-40 - An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer. Cancer. 116:4114–4121. 2010.

32 

Zhang W, Kawanishi M, Miyake K, et al: Association between YKL-40 and adult primary astrocytoma. Cancer. 116:2688–2697. 2010.PubMed/NCBI

33 

Iwamoto FM, Hottinger AF, Karimi S, et al: Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas. Neuro Oncol. 13:1244–1251. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Bernardi D, Padoan A, Ballin A, et al: Serum YKL-40 following resection for cerebral glioblastoma. J Neurooncol. 107:299–305. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Akiyama Y, Ashizawa T, Komiyama M, Miyata H, Oshita C, Omiya M, Iizuka A, Kume A, Sugino T, Hayashi N, Hayashi N, et al: YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line. Oncol Rep 32: 159-166, 2014.
APA
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M. ... Yamaguchi, K. (2014). YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line. Oncology Reports, 32, 159-166. https://doi.org/10.3892/or.2014.3195
MLA
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M., Iizuka, A., Kume, A., Sugino, T., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line". Oncology Reports 32.1 (2014): 159-166.
Chicago
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M., Iizuka, A., Kume, A., Sugino, T., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line". Oncology Reports 32, no. 1 (2014): 159-166. https://doi.org/10.3892/or.2014.3195
Copy and paste a formatted citation
x
Spandidos Publications style
Akiyama Y, Ashizawa T, Komiyama M, Miyata H, Oshita C, Omiya M, Iizuka A, Kume A, Sugino T, Hayashi N, Hayashi N, et al: YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line. Oncol Rep 32: 159-166, 2014.
APA
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M. ... Yamaguchi, K. (2014). YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line. Oncology Reports, 32, 159-166. https://doi.org/10.3892/or.2014.3195
MLA
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M., Iizuka, A., Kume, A., Sugino, T., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line". Oncology Reports 32.1 (2014): 159-166.
Chicago
Akiyama, Y., Ashizawa, T., Komiyama, M., Miyata, H., Oshita, C., Omiya, M., Iizuka, A., Kume, A., Sugino, T., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line". Oncology Reports 32, no. 1 (2014): 159-166. https://doi.org/10.3892/or.2014.3195
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