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High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors

  • Authors:
    • Yu Ikezono
    • Hironori Koga
    • Mitsuhiko Abe
    • Jun Akiba
    • Akihiko Kawahara
    • Takafumi Yoshida
    • Toru Nakamura
    • Hideki Iwamoto
    • Hirohisa Yano
    • Masayoshi Kage
    • Michio Sata
    • Osamu Tsuruta
    • Takuji Torimura
  • View Affiliations / Copyright

    Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, Department of Pathology, Kurume University School of Medicine, Kurume, Japan, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan
    Copyright: © Ikezono et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2015-2020
    |
    Published online on: July 20, 2015
       https://doi.org/10.3892/ol.2015.3513
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Abstract

Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein, is known to regulate neuronal differentiation, migration and neurogenesis. Recent evidence suggests that the protein is a putative marker for intestinal and pancreatic stem cells, including their cancer stem cell counterparts. The present study conducted immunohistochemical analyses for DCLK1 and the stemness marker, NANOG, in human intestinal neuroendocrine tumors (NETs), as their expression had not been previously investigated in these tumors. Eighteen patients with endoscopically resected rectal NETs were enrolled in the study. The mean age of the patients was 51 years old. The mean diameter of the resected tumors was 5.2 mm, and a histological diagnosis of NET grade G1 was formed for all tumors. Immunohistochemical analysis was performed not only for DCLK1, but also for the known NET markers, synaptophysin, chromogranin A and cluster of differentiation (CD)56. The intensity and distribution of staining were scored on a scale of 0‑3 and 0‑2, respectively. The sum of the scores was calculated for each specimen. Co‑expression of DCLK1 and NANOG was also examined. The mean scores for DCLK1 and synaptophysin were significantly higher than those for chromogranin A (P<0.0001) and CD56 (P<0.01). There were no significant differences in the scores between DCLK1 and synaptophysin or between chromogranin A and CD56. Notably, NANOG was expressed in high quantities in all the tumor tissues studied, showing clear co‑expression with DCLK1. In conclusion, DCLK1 may be a novel marker for rectal NET, potentially indicating the presence of the stemness gene product, NANOG.
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1 

Pearse AG: The diffuse neuroendocrine system and the apud concept: Related ‘endocrine’ peptides in brain, intestine, pituitary, placenta, and anuran cutaneous glands. Med Biol. 55:115–125. 1977.PubMed/NCBI

2 

Ito T, Igarashi H, Nakamura K, Sasano H, Okusaka T, Takano K, Komoto I, Tanaka M, Imamura M, Jensen RT, et al: Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: A nationwide survey analysis. J Gastroenterol. 50:58–64. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Tsikitis VL, Wertheim BC and Guerrero MA: Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: A seer analysis. J Cancer. 3:292–302. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Soga J: Carcinoids and their variant endocrinomas. An analysis of 11842 reported cases. J Exp Clin Cancer Res. 22:517–530. 2003.PubMed/NCBI

5 

Konishi T, Watanabe T, Kishimoto J, Kotake K, Muto T and Nagawa H: Japanese Society for Cancer of the Colon and Rectum: Prognosis and risk factors of metastasis in colorectal carcinoids: Results of a nationwide registry over 15-years. Gut. 56:863–868. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Oberndorfer S: Karzinoide Tumoren des Dünndarms. Frankf Z Pathol. 1:426–432. 1907.

7 

Rindi G, Arnold R, Bosman FT, et al: Nomenclature and classification of neuroendocrine neoplasms of digestive systemWHO Classification of Tumours of the Digestive System. Bosman FT, Carneiro F, Hruban R and Theise ND: 4th. IARC; Lyon, France: pp. 13–14. 2010

8 

Jann H, Roll S, Couvelard A, Hentic O, Pavel M, Müller-Nordhorn J, Koch M, Röcken C, Rindi G, Ruszniewski P, et al: Neuroendocrine tumors of midgut and hindgut origin: Tumor-node-metastasis classification determines clinical outcome. Cancer. 117:3332–3341. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Shu T, Tseng HC, Sapir T, Stern P, Zhou Y, Sanada K, Fischer A, Coquelle FM, Reiner O and Tsai LH: Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. Neuron. 49:25–39. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Koizumi H, Tanaka T and Gleeson JG: Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration. Neuron. 49:55–66. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Koizumi H, Higginbotham H, Poon T, Tanaka T, Brinkman BC and Gleeson JG: Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Nat Neurosci. 9:779–786. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Verissimo CS, Molenaar JJ, Meerman J, Puigvert JC, Lamers F, Koster J, Danen EH, van de Water B, Versteeg R, Fitzsimons CP, et al: Silencing of the microtubule-associated proteins doublecortin-like and doublecortin-like kinase-long induces apoptosis in neuroblastoma cells. Endocr Relat Cancer. 17:399–414. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Giannakis M, Stappenbeck TS, Mills JC, Leip DG, Lovett M, Clifton SW, Ippolito JE, Glasscock JI, Arumugam M, Brent MR, et al: Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J Biol Chem. 281:11292–11300. 2006. View Article : Google Scholar : PubMed/NCBI

14 

May R, Sureban SM, Lightfoot SA, Hoskins AB, Brackett DJ, Postier RG, Ramanujam R, Rao CV, Wyche JH, Anant S, et al: Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. Am J Physiol Gastrointest Liver Physiol. 299:G303–G310. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, Nakanishi N, Kanda K, Komekado H, Kawada M, et al: Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 45:98–103. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Bailey JM, Alsina J, Rasheed ZA, McAllister FM, Fu YY, Plentz R, Zhang H, Pasricha PJ, Bardeesy N, Matsui W, et al: DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology. 146:245–256. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Sureban SM, May R, Ramalingam S, Subramaniam D, Natarajan G, Anant S and Houchen CW: Selective blockade of DCAMKL-1 results in tumor growth arrest by a Let-7a MicroRNA-dependent mechanism. Gastroenterology. 137:649–659. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Reiner O, Coquelle FM, Peter B, Levy T, Kaplan A, Sapir T, Orr I, Barkai N, Eichele G and Bergmann S: The evolving doublecortin (DCX) superfamily. BMC Genomics. 7:1882006. View Article : Google Scholar : PubMed/NCBI

19 

Verissimo CS, Cheng S, Puigvert JC, Qin Y, Vroon A, van Deutekom J, Price LS, Danen EH, van de Water B, Fitzsimons CP, et al: Combining doublecortin-like kinase silencing and vinca alkaloids results in a synergistic apoptotic effect in neuroblastoma cells. J Pharmacol Exp Ther. 342:119–130. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Sureban SM, May R, Qu D, Weygant N, Chandrakesan P, Ali N, Lightfoot SA, Pantazis P, Rao CV, Postier RG, et al: DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. PLoS One. 8:e739402013. View Article : Google Scholar : PubMed/NCBI

21 

Gao W, Liu SM, Lu HZ, Liang J, Yuan YL and Liu XY: Analysis of clinicopathological features of intestinal neuroendocrine neoplasms. Zhonghua Zhong Liu Za Zhi. 34:450–456. 2012.(In Chinese). PubMed/NCBI

22 

Heverhagen AE, Geis C, Fendrich V, Ramaswamy A, Montalbano R, Di Fazio P, Bartsch DK, Ocker M and Quint K: Embryonic transcription factors CDX2 and Oct4 are overexpressed in neuroendocrine tumors of the ileum: A pilot study. Eur Surg Res. 51:14–20. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Sholl LM, Long KB and Hornick JL: Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 18:55–61. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Weygant N, Qu D, Berry WL, May R, Chandrakesan P, Owen DB, Sureban SM, Ali N, Janknecht R and Houchen CW: Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1. Mol Cancer. 13:1032014. View Article : Google Scholar : PubMed/NCBI

25 

Sureban SM, May R, Weygant N, Qu D, Chandrakesan P, BannermanMenson E, Ali N, Pantazis P, Westphalen CB, Wang TC, et al: XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 351:151–161. 2014. View Article : Google Scholar : PubMed/NCBI

26 

May R, Qu D, Weygant N, Chandrakesan P, Ali N, Lightfoot SA, Li L, Sureban SM and Houchen CW: Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair after radiation injury. Stem Cells. 32:822–827. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Westphalen CB, Asfaha S, Hayakawa Y, Takemoto Y, Lukin DJ, Nuber AH, Brandtner A, Setlik W, Remotti H, Muley A, et al: Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J Clin Invest. 124:1283–1295. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ikezono Y, Koga H, Abe M, Akiba J, Kawahara A, Yoshida T, Nakamura T, Iwamoto H, Yano H, Kage M, Kage M, et al: High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors. Oncol Lett 10: 2015-2020, 2015.
APA
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T. ... Torimura, T. (2015). High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors. Oncology Letters, 10, 2015-2020. https://doi.org/10.3892/ol.2015.3513
MLA
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T., Nakamura, T., Iwamoto, H., Yano, H., Kage, M., Sata, M., Tsuruta, O., Torimura, T."High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors". Oncology Letters 10.4 (2015): 2015-2020.
Chicago
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T., Nakamura, T., Iwamoto, H., Yano, H., Kage, M., Sata, M., Tsuruta, O., Torimura, T."High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors". Oncology Letters 10, no. 4 (2015): 2015-2020. https://doi.org/10.3892/ol.2015.3513
Copy and paste a formatted citation
x
Spandidos Publications style
Ikezono Y, Koga H, Abe M, Akiba J, Kawahara A, Yoshida T, Nakamura T, Iwamoto H, Yano H, Kage M, Kage M, et al: High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors. Oncol Lett 10: 2015-2020, 2015.
APA
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T. ... Torimura, T. (2015). High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors. Oncology Letters, 10, 2015-2020. https://doi.org/10.3892/ol.2015.3513
MLA
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T., Nakamura, T., Iwamoto, H., Yano, H., Kage, M., Sata, M., Tsuruta, O., Torimura, T."High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors". Oncology Letters 10.4 (2015): 2015-2020.
Chicago
Ikezono, Y., Koga, H., Abe, M., Akiba, J., Kawahara, A., Yoshida, T., Nakamura, T., Iwamoto, H., Yano, H., Kage, M., Sata, M., Tsuruta, O., Torimura, T."High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors". Oncology Letters 10, no. 4 (2015): 2015-2020. https://doi.org/10.3892/ol.2015.3513
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