Open Access

Selectively high efficacy of eribulin against high‑grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck

  • Authors:
    • Yutaka Kobayashi
    • Hiroko Kitahara
    • Mariko Hirai
    • Akira Tanaka
    • Rei Jokaji
    • Kazuhiko Kobayashi
    • George Bou‑Gharios
    • Hiroyuki Nakamura
    • Shuichi Kawashiri
  • View Affiliations

  • Published online on: March 19, 2019     https://doi.org/10.3892/ol.2019.10165
  • Pages: 5064-5072
  • Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have a poor prognosis. Over the past decade, a major development in the first‑line treatment of R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5‑fluorouracil chemotherapy. Currently, a promising novel treatment option in R/M SCCHN has emerged, termed immune checkpoint inhibitors. However, only a few patients presenting with R/M SCCHN have exhibited meaningful tumor regression with these agents. Therefore, novel agents are required to order improve the overall survival of patients with R/M SCCHN. Recently, we demonstrated that R/M SCCHN cells are highly sensitive to eribulin. In the present study, the effects of eribulin, paclitaxel and vinblastine were investigated in R/M SCCHN (OLC‑01 and OSC‑19) and locally advanced SCCHN (OSC‑20) cells. Tumour‑inhibitory activities of eribulin against R/M SCCHN were evaluated in orthotopic xenograft models. The data revealed that eribulin has sub‑nM growth inhibitory activities in vitro against OLC‑01 cells, and that it is more potent than paclitaxel and vinblastine. The reduced expression of Tubulin Beta 3 Class III (TUBB3) following treatment was correlated with a high sensitivity to eribulin. Histological analysis of OLC‑01 cells in NOD‑SCID mice demonstrated that they had a higher invasiveness in the tissue around the alveolar cancer when compared with the histology of OSC‑19 cells, which has been reported in our previous study. Treatment with eribulin revealed marked inhibitory activities in vivo at 0.125 mg/kg against OLC‑01 cells orthotopic xenografts. In conclusion, the results highlight the existence of invasive‑type heterogeneity in R/M SCCHN with respect to eribulin sensitivity. Eribulin is already an approved clinical agent; therefore, the continued investigation of its preclinical antitumor attributes may contribute significantly to the future process of identifying novel uses of eribulin against R/M SCCHN.

References

1 

Price KA and Cohen EE: Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 13:35–46. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Vermorken JB and Specenier P: Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol. 21 Suppl:vii252–vii261. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 359:1116–1127. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Guigay J, Fayette J, Dillies AF, Sire C, Kerger JN, Tennevet I, Machiels JP, Zanetta S, Pointreau Y, Bozec Le Moal L, et al: Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A multicenter, phase II GORTEC study. Ann Oncol. 26:1941–1947. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Tahara M, Kiyota N, Yokota T, Hasegawa Y, Muro K, Takahashi S, Onoe T, Homma A, Taguchi J, Suzuki M, et al: Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). Ann Oncol. 29:1004–1009. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, et al: Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 375:1856–1867. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, Kasper S, Even C, Vokes EE, Worden F, et al: Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): Health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 18:1104–1115. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Saada-Bouzid E, Defaucheux C, Karabajakian A, Coloma VP, Servois V, Paoletti X, Even C, Fayette J, Guigay J, Loirat D, et al: Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 28:1605–1611. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, et al: In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 61:1013–1021. 2001.PubMed/NCBI

10 

Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA and Wilson L: The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 4:1086–1095. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Okouneva T, Azarenko O, Wilson L, Littlefield BA and Jordan MA: Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase. Mol Cancer Ther. 7:2003–2011. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA and Jordan MA: Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 49:1331–1337. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ and Littlefield BA: Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 64:5760–5766. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ and Littlefield BA: Eribulin induces irreversible mitotic blockade: Implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions. Cancer Res. 71:496–505. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Kitahara H, Hirai M, Kato K, Bou-Gharios G, Nakamura H and Kawashiri S: Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. Oncol Rep. 36:3139–3144. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE and Cortes J: Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 33:594–601. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Yokoi T, Homma H and Odajima T: Establishment and characterization of OSC-19 cell line in serum and protein free culture. Tumor Res. 24:1–17. 1988.

18 

Kawashiri S, Noguchi N, Tanaka A, Nakaya H, Kato K and Yamamoto E: Inhibitory effect of neoadjuvant chemotherapy on metastasis of oral squamous cell carcinoma in a mouse model. Oral Oncol. 45:794–797. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Yokoi T, Hirata S, Nishimura F, Miyakawa A, Odajima T and Kohama G: Some properties of a newly established human cell line derived from an oral squamous carcinoma. Tumor Res. 25:93–91-93. 1990.

20 

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 : PubMed/NCBI

21 

Jordan MA and Wilson L: Microtubules as a target for anticancer drugs. Nat Rev Cancer. 4:253–265. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Bai R, Nguyen TL, Burnett JC, Atasoylu O, Munro MH, Pettit GR, Smith AB III, Gussio R and Hamel E: Interactions of halichondrin B and eribulin with tubulin. J Chem Inf Model. 51:1393–1404. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Nogales E, Wolf SG, Khan IA, Luduena RF and Downing KH: Structure of tubulin at 6.5 A and location of the taxol-binding site. Nature. 375:424–427. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Bai RL, Pettit GR and Hamel E: Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. J Biol Chem. 265:17141–17149. 1990.PubMed/NCBI

25 

Dezső Z, Oestreicher J, Weaver A, Santiago S, Agoulnik S, Chow J, Oda Y and Funahashi Y: Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells. PLoS One. 9:e1061312014. View Article : Google Scholar : PubMed/NCBI

26 

Mendelsohn W: The significance of abnormal mitosis in the development of malignancy. Am J Cancer. 24:626–636. 1935.

27 

Miki S, Imamichi S, Fujimori H, Tomiyama A, Fujimoto K, Satomi K, Matsushita Y, Matsuzaki S, Takahashi M, Ishikawa E, et al: Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma. Cancer Sci. 109:2275–2285. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Swami U, Chaudhary I, Ghalib MH and Goel S: Eribulin-A review of preclinical and clinical studies. Crit Rev Oncol Hematol. 81:163–184. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Wilson L, Lopus M, Miller HP, Azarenko O, Riffle S, Smith JA and Jordan MA: Effects of eribulin on microtubule binding and dynamic instability are strengthened in the absence of the beta III tubulin isotype. Biochemistry. 54:6482–6489. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Person F, Wilczak W, Hube-Magg C, Burdelski C, Möller-Koop C, Simon R, Noriega M, Sauter G, Steurer S, Burdak-Rothkamm S and Jacobsen F: Prevalence of beta III-tubulin (TUBB3) expression in human normal tissues and cancers. Tumour Biol. 39:10104283177121662017. View Article : Google Scholar : PubMed/NCBI

31 

Koh Y, Jang B, Han SW, Kim TM, Oh DY, Lee SH, Kang CH, Kim DW, Im SA, Chung DH, et al: Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer. J Thorac Oncol. 5:320–325. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Lebok P, Ozturk M, Heilenkotter U, Jaenicke F, Müller V, Paluchowski P, Geist S, Wilke C, Burandt E, Lebeau A, et al: High levels of class III beta-tubulin expression are associated with aggressive tumor features in breast cancer. Oncol Lett. 11:1987–1994. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Hinsch A, Chaker A, Burdelski C, Koop C, Tsourlakis MC, Steurer S, Rink M, Eichenauer TS, Wilczak W, Wittmer C, et al: βIII-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer. Hum Pathol. 61:210–220. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Loeser H, Schallenberg S, von Winterfeld M, Tharun L, Alakus H, Hölscher A, Bollschweiler E, Buettner R, Zander T and Quaas A: High protein and mRNA expression levels of TUBB3 (class III ss-tubulin) are associated with aggressive tumor features in esophageal adenocarcinomas. Oncotarget. 8:115179–115189. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Nienstedt JC, Grobe A, Clauditz T, Simon R, Muenscher A, Knecht R, Sauter G, Moebius C, Blessmann M, Heiland M and Pflug C: High-level betaIII-tubulin overexpression occurs in most head and neck cancers but is unrelated to clinical outcome. J Oral Pathol Med. 46:986–990. 2017.PubMed/NCBI

36 

Bachurski CJ, Theodorakis NG, Coulson RM and Cleveland DW: An amino-terminal tetrapeptide specifies cotranslational degradation of beta-tubulin but not alpha-tubulin mRNAs. Mol Cell Biol. 14:4076–4086. 1994. View Article : Google Scholar : PubMed/NCBI

37 

Stargell LA, Heruth DP, Gaertig J and Gorovsky MA: Drugs affecting microtubule dynamics increase alpha-tubulin mRNA accumulation via transcription in Tetrahymena thermophila. Mol Cell Biol. 12:1443–1450. 1992. View Article : Google Scholar : PubMed/NCBI

38 

Arnold SM, Moon J, Williamson SK, Atkins JN, Ou SH, LeBlanc M and Urba SG: Phase II evaluation of eribulin mesylate (E7389, NSC 707389) in patients with metastatic or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group trial S0618. Invest New Drugs. 29:352–359. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kobayashi, Y., Kitahara, H., Hirai, M., Tanaka, A., Jokaji, R., Kobayashi, K. ... Kawashiri, S. (2019). Selectively high efficacy of eribulin against high‑grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck. Oncology Letters, 17, 5064-5072. https://doi.org/10.3892/ol.2019.10165
MLA
Kobayashi, Y., Kitahara, H., Hirai, M., Tanaka, A., Jokaji, R., Kobayashi, K., Bou‑Gharios, G., Nakamura, H., Kawashiri, S."Selectively high efficacy of eribulin against high‑grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck". Oncology Letters 17.6 (2019): 5064-5072.
Chicago
Kobayashi, Y., Kitahara, H., Hirai, M., Tanaka, A., Jokaji, R., Kobayashi, K., Bou‑Gharios, G., Nakamura, H., Kawashiri, S."Selectively high efficacy of eribulin against high‑grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck". Oncology Letters 17, no. 6 (2019): 5064-5072. https://doi.org/10.3892/ol.2019.10165