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Article

TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer

  • Authors:
    • Zhuo Deng
    • Jiancheng Zhou
    • Xi Han
    • Xu Li
  • View Affiliations / Copyright

    Affiliations: Center for Translational Medicine and, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
  • Pages: 359-365
    |
    Published online on: November 3, 2015
       https://doi.org/10.3892/or.2015.4388
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Abstract

Targeted therapy has revolutionized the therapeutic landscape in oncology in recent years and anti-VEGF agent has been approved for ovarian cancer (OC). Unfortunately, the efficacy of this treatment is limited due to the development of resistance, while the molecular mechanisms underlying OC resistance to anti-VEGF therapy are less clear. In this study, we observed a differential response of OC cells to anti-VEGF agent bevacizumab (BV) by using xenograft models. Gene expression analysis showed that TCEB2 gene was significantly upregulated in the OC tumors with acquired resistance compared with the sensitive tumors. Further mechanism dissections demonstrated that TCEB2 played a critical role in the development of acquired resistance to BV in OC cells via promoting HIF-1α degradation and suppressing VEGF-A expression. In TCEB2 overexpressing cells, interleukin-8 (IL-8) was elevated and functioned as a compensatory angiogenesis signaling which was sensitive to IL-8 monoclonal antibody (IL-8 Ab). The combination of BV and IL-8 Ab exhibited synergistic effect of growth inhibition on both OC and endothelial cells. Thus, this study provides an alternative strategy of simultaneously targeting VEGF-A and IL-8 for combating OC.
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1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Sonoda Y: Management of early ovarian cancer. Oncology (Williston Park). 18:343–362. 2004.

3 

Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, Aoki D, Jobo T, Kodama S, Terauchi F, et al Japanese Gynecologic Oncology Group: Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): A randomised, controlled, open-label trial. Lancet Oncol. 14:1020–1026. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al: Rethinking ovarian cancer: Recommendations for improving outcomes. Nat Rev Cancer. 11:719–725. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Coward JI, Middleton K and Murphy F: New perspectives on targeted therapy in ovarian cancer. Int J Womens Health. 7:189–203. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Teplinsky E and Muggia F: Targeting HER2 in ovarian and uterine cancers: Challenges and future directions. Gynecol Oncol. 135:364–370. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Bamberger ES and Perrett CW: Angiogenesis in epithelian ovarian cancer. Mol Pathol. 55:348–359. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Longo R, Sarmiento R, Fanelli M, Capaccetti B, Gattuso D and Gasparini G: Anti-angiogenic therapy: Rationale, challenges and clinical studies. Angiogenesis. 5:237–256. 2002. View Article : Google Scholar

9 

Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, et al: Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 25:5180–5186. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Garcia AA, Hirte H, Fleming G, Yang D, Tsao-Wei DD, Roman L, Groshen S, Swenson S, Markland F, Gandara D, et al: Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol. 26:76–82. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Spannuth WA, Sood AK and Coleman RL: Angiogenesis as a strategic target for ovarian cancer therapy. Nat Clin Pract Oncol. 5:194–204. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Garrett KP, Aso T, Bradsher JN, Foundling SI, Lane WS, Conaway RC and Conaway JW: Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog. Proc Natl Acad Sci USA. 92:7172–7176. 1995. View Article : Google Scholar : PubMed/NCBI

13 

Stebbins CE, Kaelin WG Jr and Pavletich NP: Structure of the VHL-ElonginC-ElonginB complex: Implications for VHL tumor suppressor function. Science. 284:455–461. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Zhou J, Wu K, Gao D, Zhu G, Wu D, Wang X, Chen Y, Du Y, Song W, Ma Z, et al: Reciprocal regulation of hypoxia-inducible factor 2α and GLI1 expression associated with the radiore-sistance of renal cell carcinoma. Int J Radiat Oncol Biol Phys. 90:942–951. 2014. View Article : Google Scholar

15 

Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, et al: Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. J Clin Invest. 121:1313–1328. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Ke Q and Costa M: Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol. 70:1469–1480. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Grepin R, Guyot M, Jacquin M, Durivault J, Chamorey E, Sudaka A, Serdjebi C, Lacarelle B, Scoazec JY, Negrier S, et al: Acceleration of clear cell renal cell carcinoma growth in mice following bevacizumab/Avastin treatment: The role of CXCL cytokines. Oncogene. 31:1683–1694. 2012. View Article : Google Scholar

18 

Huang D, Ding Y, Zhou M, Rini BI, Petillo D, Qian CN, Kahnoski R, Futreal PA, Furge KA and Teh BT: Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. Cancer Res. 70:1063–1071. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Abraham RT: Chemokine to the rescue: Interleukin-8 mediates resistance to PI3K-pathway-targeted therapy in breast cancer. Cancer Cell. 22:703–705. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, et al: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 27:740–745. 2009. View Article : Google Scholar :

21 

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R and Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 355:2542–2550. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S and Sneller V: Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. J Clin Oncol. 28:2144–2150. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, et al Gynecologic Oncology Group: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 365:2473–2483. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, et al ICON7 Investigators: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 365:2484–2496. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, et al: Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 32:1302–1308. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, et al AVOREN Trial investigators: Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet. 370:2103–2111. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Shojaei F, Lee JH, Simmons BH, Wong A, Esparza CO, Plumlee PA, Feng J, Stewart AE, Hu-Lowe DD and Christensen JG: HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res. 70:10090–10100. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Figlin RA, Kaufmann I and Brechbiel J: Targeting PI3K and mTORC2 in metastatic renal cell carcinoma: New strategies for overcoming resistance to VEGFR and mTORC1 inhibitors. Int J Cancer. 133:788–796. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al: Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 481:380–384. 2012.

31 

Smerdel MP, Steffensen KD, Waldstrøm M, Brandslund I and Jakobsen A: The predictive value of serum VEGF in multi-resistant ovarian cancer patients treated with bevacizumab. Gynecol Oncol. 118:167–171. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Haase VH: The VHL tumor suppressor: Master regulator of HIF. Curr Pharm Des. 15:3895–3903. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Horwitz E, Stein I, Andreozzi M, Nemeth J, Shoham A, Pappo O, Schweitzer N, Tornillo L, Kanarek N, Quagliata L, et al: Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. Cancer Discov. 4:730–743. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Deng Z, Zhou J, Han X and Li X: TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncol Rep 35: 359-365, 2016.
APA
Deng, Z., Zhou, J., Han, X., & Li, X. (2016). TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncology Reports, 35, 359-365. https://doi.org/10.3892/or.2015.4388
MLA
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35.1 (2016): 359-365.
Chicago
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35, no. 1 (2016): 359-365. https://doi.org/10.3892/or.2015.4388
Copy and paste a formatted citation
x
Spandidos Publications style
Deng Z, Zhou J, Han X and Li X: TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncol Rep 35: 359-365, 2016.
APA
Deng, Z., Zhou, J., Han, X., & Li, X. (2016). TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncology Reports, 35, 359-365. https://doi.org/10.3892/or.2015.4388
MLA
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35.1 (2016): 359-365.
Chicago
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35, no. 1 (2016): 359-365. https://doi.org/10.3892/or.2015.4388
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