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Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway

  • Authors:
    • Hong‑Kuan Yang
    • Hao Chen
    • Feng Mao
    • Qun‑Gen Xiao
    • Rui‑Fan Xie
    • Ting Lei
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4021-4028
    |
    Published online on: July 26, 2017
       https://doi.org/10.3892/ol.2017.6671
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Abstract

Active angiogenesis is the basic pathological feature of glioma. Tumor angiogenesis is involved in vascular endothelial cell migration to the tumor tissue and in the formation of tube‑like structures. The present study aimed to investigate the role of leucine‑rich repeats and immunoglobulin‑like domains 2 (LRIG2) in glioma angiogenesis. Glioma (n=50) and normal brain (n=20) tissue samples were collected from patients to detect the expression of LRIG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGF‑A), and cluster of differentiation 31 (CD31) using immunohistochemistry. In addition, the association between the expression of LRIG2 in glioma tissue and the microvessel density (MVD) was analyzed. In vitro, the expression of LRIG2 in human glioma U87 and U251 cell lines was knocked down. Subsequently, cell migration and tube formation assays of human umbilical vein endothelial cells (HUVECs) were performed using a coculture system. The protein expression levels of LRIG2, EGFR, phosphorylated‑EGFR and VEGF‑A were determined using western blotting. The results demonstrated that the expression levels of LRIG2, EGFR, VEGF‑A and CD31 were highly upregulated in glioma tissue samples. Furthermore, LRIG2 expression in glioma tissue samples was significantly correlated with the MVD. In vitro, the downregulation of LRIG2 inhibited HUVEC migration and tube formation induced by coculture with glioma cells. The downregulation of LRIG2 resulted in decreased expression of EGFR and VEGF‑A. The effects of the LRIG2 knockdown were reversed following EGF treatment. These findings suggest that LRIG2 is a potential target for the inhibition of glioma angiogenesis, which is possibly mediated via the EGFR/VEGF‑A signaling pathway.
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1 

Wen PY and Reardon DA: Neuro-oncology in 2015: Progress in glioma diagnosis, classification and treatment. Nat Rev Neurol. 12:69–70. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Malla RR, Gopinath S, Gondi CS, Alapati K, Dinh DH, Gujrati M and Rao JS: Cathepsin B and uPAR knockdown inhibits tumor-induced angiogenesis by modulating VEGF expression in glioma. Cancer Gene Ther. 18:419–434. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Babykutty S SPPJNR, Kumar MA, Nair MS, Srinivas P and Gopala S: Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP-2/9 expression via inhibiting ERK1/2 and reducing DNA-binding activity of NF-κB in colon cancer cells. Mol Carcinog. 51:475–490. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Petrillo M, Borriello M, Fuoco G, Legge F, Iannone V and Ferrandina G: Novel VEGF-independent strategies targeting tumor vasculature: Clinical aspects. Curr Pharm Des. 18:2702–2712. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Reardon DA, Turner S, Peters KB, Desjardins A, Gururangan S, Sampson JH, McLendon RE, Herndon JE II, Jones LW, Kirkpatrick JP, et al: A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma. J Natl Compr Canc Netw. 9:414–427. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Cea V, Sala C and Verpelli C: Antiangiogenic therapy for glioma. J Signal Transduct. 2012:4830402012. View Article : Google Scholar : PubMed/NCBI

7 

Casaletto JB and McClatchey AI: Spatial regulation of receptor tyrosine kinases in development and cancer. Nat Rev Cancer. 12:387–400. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Larsen AK, Ouaret D, El Ouadrani K and Petitprez A: Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol Ther. 131:80–90. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Malik U and Javed A: LRIGs: A prognostically significant family with emerging therapeutic competence against cancers. Curr Cancer Drug Targets. 17:3–16. 2017. View Article : Google Scholar : PubMed/NCBI

10 

van Erp S, van den Heuvel DM, Fujita Y, Robinson RA, Hellemons AJ, Adolfs Y, Van Battum EY, Blokhuis AM, Kuijpers M, Demmers JA, et al: Lrig2 negatively regulates ectodomain shedding of Axon guidance receptors by ADAM proteases. Dev Cell. 35:537–552. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Guo D, Nilsson J, Haapasalo H, Raheem O, Bergenheim T, Hedman H and Henriksson R: Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. Acta Neuropathol. 111:238–246. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Lindström AK, Asplund A and Hellberg D: Correlation between LRIG1 and LRIG2 expressions and expression of 11 tumor markers, with special reference to tumor suppressors, in CIN and normal cervical epithelium. Gynecol Oncol. 122:372–376. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, Higginbotham JN, Juchheim A, Prasad N, Levy SE, et al: The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell. 149:146–158. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Wong VW, Stange DE, Page ME, Buczacki S, Wabik A, Itami S, van de Wetering M, Poulsom R, Wright NA, Trotter MW, et al: Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat Cell Biol. 14:401–408. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Lu L, Teixeira VH, Yuan Z, Graham TA, Endesfelder D, Kolluri K, Al-Juffali N, Hamilton N, Nicholson AG, Falzon M, et al: LRIG1 regulates cadherin-dependent contact inhibition directing epithelial homeostasis and pre-invasive squamous cell carcinoma development. J Pathol. 229:608–620. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Bai L, McEachern D, Yang CY, Lu J, Sun H and Wang S: LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling. Cancer Res. 72:1229–1238. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Hedman H, Lindström AK, Tot T, Stendahl U, Henriksson R and Hellberg D: LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix. Acta Oncol. 49:812–815. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Holmlund C, Haapasalo H, Yi W, Raheem O, Brännström T, Bragge H, Henriksson R and Hedman H: Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival. Neuropathology. 29:242–247. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Wang B, Han L, Chen R, Cai M, Han F, Lei T and Guo D: Downregulation of LRIG2 expression by RNA interference inhibits glioblastoma cell (GL15) growth, causes cell cycle redistribution, increases cell apoptosis and enhances cell adhesion and invasion in vitro. Cancer Biol Ther. 8:1018–1023. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Remmele W and Stegner HE: Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 8:138–140. 1987.(In German). PubMed/NCBI

21 

Tai YT, Acharya C, An G, Moschetta M, Zhong MY, Feng X, Cea M, Cagnetta A, Wen K, van Eenennaam H, et al: APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 127:3225–3236. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Wang G, Wu J and Song H: LRIG2 expression and prognosis in non-small cell lung cancer. Oncol Lett. 8:667–672. 2014.PubMed/NCBI

23 

Cui L, Xu S, Song Z, Zhao G, Liu X and Song Y: Pituitary tumor transforming gene: A novel therapeutic target for glioma treatment. Acta Biochim Biophys Sin (Shanghai). 47:414–421. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Jiang T, Qiao M, Zhou F, Ren S, Su C and Zhou C: Effect of combined therapy inhibiting EGFR and VEGFR pathways in non-small-cell lung cancer on progression-free and overall survival. Clin Lung Cancer. Dec 29–2016.(Epub ahead of print).

25 

Yu X, Li W, Deng Q, You S, Liu H, Peng S, Liu X, Lu J, Luo X, Yang L, et al: Neoalbaconol inhibits angiogenesis and tumor growth by suppressing EGFR-mediated VEGF production. Mol Carcinog. 56:1414–1426. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang HK, Chen H, Mao F, Xiao QG, Xie RF and Lei T: Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway. Oncol Lett 14: 4021-4028, 2017.
APA
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., & Lei, T. (2017). Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway. Oncology Letters, 14, 4021-4028. https://doi.org/10.3892/ol.2017.6671
MLA
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., Lei, T."Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway". Oncology Letters 14.4 (2017): 4021-4028.
Chicago
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., Lei, T."Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway". Oncology Letters 14, no. 4 (2017): 4021-4028. https://doi.org/10.3892/ol.2017.6671
Copy and paste a formatted citation
x
Spandidos Publications style
Yang HK, Chen H, Mao F, Xiao QG, Xie RF and Lei T: Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway. Oncol Lett 14: 4021-4028, 2017.
APA
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., & Lei, T. (2017). Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway. Oncology Letters, 14, 4021-4028. https://doi.org/10.3892/ol.2017.6671
MLA
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., Lei, T."Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway". Oncology Letters 14.4 (2017): 4021-4028.
Chicago
Yang, H., Chen, H., Mao, F., Xiao, Q., Xie, R., Lei, T."Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF‑A pathway". Oncology Letters 14, no. 4 (2017): 4021-4028. https://doi.org/10.3892/ol.2017.6671
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