Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-05-22T21:02:56.199Z Has data issue: false hasContentIssue false

The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

Published online by Cambridge University Press:  23 September 2014

Wenhao Wu
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Yongji Tian
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Hong Wan
Affiliation:
Department of Biochemistry, Beijing Neurosurgical Institute, Capital Medical University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Yongmei Song
Affiliation:
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Junhua Li
Affiliation:
Department of Biochemistry, Beijing Neurosurgical Institute, Capital Medical University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Liwei Zhang*
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
*
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing, 100050, P.R. China. email: zhangliweittyy@yahoo.com.cn
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.

Methods:

This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.

Results:

Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.

Conclusions:

Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

Contexte:

Le pronostic général des gliomes du tronc cérébral est très mauvais et le traitement actuel ne prolonge pas significativement la survie de ces patients. Il est donc important d'étudier les mécanismes de biologie moléculaire liés à leur apparition et à leur développement afin d'en améliorer le traitement. La voie de signalisation Wnt/β-caténine est étroitement associée à l'apparition et au développement de tumeurs. Cependant, on ignore sa relation aux gliomes du tronc cérébral.

Méthode:

Dans cette étude, nous avons utilisé le buvardage Western ainsi que des méthodes d'immunohistochimie pour détecter l'expression de composantes reliées à la voie de signalisation Wnt/β-caténine, telles Wnt-1, Wnt-2, β-caténine et C-myc, dans 6 cerveaux normaux et 24 gliomes du tronc cérébral et nous avons analysé la relation entre leur expression et les caractéristiques anatomo-cliniques des tumeurs.

Résultats:

Wnt-1 n'avait pas d'expression apparente dans les tissus cérébraux normaux et il n'y avait pas de différence significative entre les gliomes du tronc cérébral de haut grade et ceux de bas grade de malignité. L'expression de Wnt-2, de β-caténine et de C-myc dans les gliomes du tronc cérébral de haut grade était significativement plus élevée que dans ceux de bas grade et dans le tissu cérébral normal, et leur expression était corrélée de façon positive à l'expression de Ki-67. De plus, l'expression de Wnt-2 et de C-myc était associée de façon significative au pronostic des patients atteints de gliomes du tronc cérébral. Une expression augmentée de β-caténine avait tendance à être associée à une survie plus courte, mais la différence n'était pas significative au point de vue statistique.

Conclusions:

Il se peut que la voie de signalisation Wnt/β-caténine soit activée de façon anormale et joue un rôle important dans l'apparition et le développement des gliomes du tronc cérébral. Wnt-2, β-caténine et C-myc pourraient constituer des cibles de traitement du gliome du tronc cérébral.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1. Laigle-Donadey, F, Doz, F, Delattre, JY. Brainstem gliomas in children and adults. Curr Opin Oncol. 2008;20(6):662–7.Google Scholar
2. Rosenthal, MA, Ashley, DM, Drummond, KJ, et al. Brain stem gliomas: patterns of care in Victoria from 1998-2000. J Clin Neurosci. 2008;15(3):237–40.Google Scholar
3. Liu, YL, Yang, HP, Zhou, XD, Gong, L, Tang, CL, Wang, HJ. The hypomethylation agent bisdemethoxycurcumin acts on the WIF-1 promoter, inhibits the canonical Wnt pathway and induces apoptosis in human non-small-cell lung cancer. Curr Cancer Drug Targets. 2011;11(9):1098–110.CrossRefGoogle ScholarPubMed
4. Yang, L, Chen, Y, Cui, T, et al. Desmoplakin acts as a tumour suppressor by inhibition of the Wnt/β-catenin signalling pathway in human lung cancer. Carcinogenesis. 2012;33(10):1863–70.Google Scholar
5. Yeh, CT, Rao, YK, Ye, M, et al. Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging. Toxicol Appl Pharmacol. 2012;261(1):3141.Google Scholar
6. Mehta, VS, Chandra, PS, Singh, PK, Garg, A, Rath, GK. Surgical considerations for ‘intrinsic’ brainstem gliomas: proposal of a modification inclassification. Neurol India. 2009;57(3):274–81.Google Scholar
7. Mohanty, A. Role of surgery in brainstem gliomas. Neurol India. 2009;57(3):231–2.Google Scholar
8. Bartels, U, Hawkins, C, Vézina, G, Kun, L, Souweidane, M, Bouffet, E. Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG. J Neurooncol. 2011;105(1):119–25.Google Scholar
9. Chassot, A, Canale, S, Varlet, P, et al. Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. J Neurooncol. 2012;106(2):399407.CrossRefGoogle ScholarPubMed
10. Kang, YJ, Park, HJ, Chung, HJ, et al. Wnt/β-Catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells. Mol Pharmacol. 2012;82(2):168–77.Google Scholar
11. Pacheco-Pinedo, EC, Durham, AC, Stewart, KM, et al. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium. J Clin Invest. 2011;121(5):1935–45.Google Scholar
12. Lachenmayer, A, Alsinet, C, Savic, R, et al. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clin Cancer Res. 2012;18(18):49975007.Google Scholar
13. Asuthkar, S, Gondi, CS, Nalla, AK, Velpula, KK, Gorantla, B, Rao, JS. Urokinase-type plasminogen activator receptor (uPAR)-mediated regulation of WNT/β-cateninsignaling is enhanced in irradiated medulloblastoma cells. J Biol Chem. 2012;287(24): 2057689.Google Scholar
14. Cimmino, F, Scoppettuolo, MN, Carotenuto, M, et al. Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling. J Neurooncol. 2012;106(1):5970.CrossRefGoogle ScholarPubMed
15. Baryawno, N, Sveinbjörnsson, B, Eksborg, S, Chen, CS, Kogner, P, Johnsen, JI. Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. Cancer Res. 2010;70(1):266–76.Google Scholar
16. Zhang, N, Wei, P, Gong, A, et al. FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis. Cancer Cell. 2011;20(4):427–42.Google Scholar
17. Rossi, M, Magnoni, L, Miracco, C, et al. β-catenin and gli1 are prognostic markers in glioblastoma. Cancer Biol Ther. 2011;11(8):753–61.Google Scholar
18. Kahlert, UD, Maciaczyk, D, Doostkam, S, et al. Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition. Cancer Lett. 2012;325(1):4253.Google Scholar
19. Logan, CY, Nusse, R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781810.Google Scholar
20. Liu, C, Tu, Y, Sun, X, et al. Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations. Clin Exp Med. 2011;11(2):105–12.Google Scholar
21. Pu, P, Zhang, Z, Kang, C, et al. Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 2009;16(4):351–61.Google Scholar
22. Sareddy, GR, Panigrahi, M, Challa, S, Mahadevan, A, Babu, PP. Activation of Wnt/beta-catenin/Tcf signaling pathway in human astrocytomas. Neurochem Int. 2009;55(5):307–17.Google Scholar