Expression of CXC-motif-chemokine 12 and the receptor C‑X‑C receptor 4 in glioma and theeffect on peritumoral brain edema

Tang,Wenlong; Chen,Yupeng; Wang,Xingfu; Chen,Yao; Zhang,Jiandong; Lin,Zhixiong

doi:10.3892/ol.2017.7547

Expression of CXC-motif-chemokine 12 and the receptor C‑X‑C receptor 4 in glioma and theeffect on peritumoral brain edema

Authors:
- Wenlong Tang
- Yupeng Chen
- Xingfu Wang
- Yao Chen
- Jiandong Zhang
- Zhixiong Lin
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
Published online on: December 8, 2017 https://doi.org/10.3892/ol.2017.7547
Pages: 2501-2507

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Abstract

The present study aimed to evaluate the association between CXC‑motif‑chemokine 12 (CXCL12)/C‑X‑C receptor 4 (CXCR4) expression and peritumoral brain edema (PTBE) in glioma patients. Immunohistochemical techniques were used to detect the expression of CXCR4 and CXCL12 in 58 glioma tissues. Magnetic resonance imaging was used to evaluate the extent and type of brain edema in preoperative glioma patients. The association between edema and CXCL12/CXCR4 expression was examined by χ2 analysis. The prognostic significance of CXCL12 or CXCR4 was determined by log‑rank tests and Cox's proportional hazards model. Expression of CXCL12 and CXCR4 was observed in vascular endothelial cells and tumor cells. The degree (P=0.033) and morphology (P=0.033) of PTBE were significantly associated with the level of CXCL12 expression in vascular endothelial cells. The degree (P=0.001) and morphology (P=0.001) of PTBE were associated with the level of CXCR4 expression in tumor cells. CXCR4‑positive vascular endothelial cells were significantly associated only with the degree of edema (P=0.030). Therefore, the present study indicated that levels of CXCL12 expression in vascular endothelial cells and CXCR4 expression in tumor cells are associated with PTBE.

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1	Seidel C, Dörner N, Osswald M, Wick A, Platten M, Bendszus M and Wick W: Does age matter?-A MRI study on peritumoral edema in newly diagnosed primary glioblastoma. BMC Cancer. 11:1272011. View Article : Google Scholar : PubMed/NCBI
2	Schoenegger K, Oberndorfer S, Wuschitz B, Struhal W, Hainfellner J, Prayer D, Heinzl H, Lahrmann H, Marosi C and Grisold W: Peritumoral edema on MRI at initial diagnosis: An independent prognostic factor for glioblastoma? Eur J Neurol. 16:874–878. 2009. View Article : Google Scholar : PubMed/NCBI
3	Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, Fang X, Sloan AE, Mao Y, Lathia JD, et al: Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 153:139–152. 2013. View Article : Google Scholar : PubMed/NCBI
4	Soda Y, Myskiw C, Rommel A and Verma IM: Mechanisms of neovascularization and resistance to anti-angiogenic therapies in glioblastoma multiforme. J Mol Med (Berl). 91:439–448. 2013. View Article : Google Scholar : PubMed/NCBI
5	Lu S, Ahn D, Johnson G, Law M, Zagzag D and Grossman RI: Diffusion-tensor MR imaging of intracranial neoplasia and associated peritumoral edema: Introduction of the tumor infiltration index. Radiology. 232:221–228. 2004. View Article : Google Scholar : PubMed/NCBI
6	Lin ZX: Glioma-related edema: New insight into molecular mechanisms and their clinical implications. Chin J Cancer. 32:49–52. 2013. View Article : Google Scholar : PubMed/NCBI
7	Hartmann M, Jansen O, Egelhof T, Forsting M, Albert FK and Sartor K: Effect of brain edema on the recurrence pattern of malignant gliomas. Radiologe. 38:948–953. 1998.(In German). View Article : Google Scholar : PubMed/NCBI
8	Engelhorn T, Savaskan NE, Schwarz MA, Kreutzer J, Meyer EP, Hahnen E, Ganslandt O, Dörfler A, Nimsky C, Buchfelder M and Eyüpoglu IY: Cellular characterization of the peritumoral edema zone in malignant brain tumors. Cancer Sci. 100:1856–1862. 2009. View Article : Google Scholar : PubMed/NCBI
9	Zhou Y, Larsen PH, Hao C and Yong VW: CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem. 277:49481–49487. 2002. View Article : Google Scholar : PubMed/NCBI
10	Bian XW, Yang SX, Chen JH, Ping YF, Zhou XD, Wang QL, Jiang XF, Gong W, Xiao HL, Du LL, et al: Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival. Neurosurgery. 61:570–579. 2007. View Article : Google Scholar : PubMed/NCBI
11	Ehtesham M, Winston JA, Kabos P and Thompson RC: CXCR4 expression mediates glioma cell invasiveness. Oncogene. 25:2801–2806. 2006. View Article : Google Scholar : PubMed/NCBI
12	Stevenson CB, Ehtesham M, McMillan KM, Valadez JG, Edgeworth ML, Price RR, Abel TW, Mapara KY and Thompson RC: CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities. Neurosurgery. 63:560–570. 2008. View Article : Google Scholar : PubMed/NCBI
13	Barbero S, Bonavia R, Bajetto A, Porcile C, Pirani P, Ravetti JL, Zona GL, Spaziante R, Florio T and Schettini G: Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. Cancer Res. 63:1969–1974. 2003.PubMed/NCBI
14	Lin ZX: Patterns in the occurrence and development of tumors. Chin Med J (Engl). 124:1097–1104. 2011.PubMed/NCBI
15	Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW and Kleihues P: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114:97–109. 2007. View Article : Google Scholar : PubMed/NCBI
16	Zagzag D, Esencay M, Mendez O, Yee H, Smirnova I, Huang Y, Chiriboga L, Lukyanov E, Liu M and Newcomb EW: Hypoxia- and vascular endothelial growth factor-induced stromal cell-derived factor-1alpha/CXCR4 expression in glioblastomas: One plausible explanation of Scherer's structures. Am J Pathol. 173:545–560. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, et al: Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 330:1066–1071. 2010. View Article : Google Scholar : PubMed/NCBI
18	Yoshie O, Imai T and Nomiyama H: Novel lymphocyte-specific CC chemokines and their receptors. J Leukoc Biol. 62:634–644. 1997. View Article : Google Scholar : PubMed/NCBI
19	Furusato B, Mohamed A, Uhlén M and Rhim JS: CXCR4 and cancer. Pathol Int. 60:497–505. 2010. View Article : Google Scholar : PubMed/NCBI
20	Sun X, Cheng G, Hao M, Zheng J, Zhou X, Zhang J, Taichman RS, Pienta KJ and Wang J: CXCL12/CXCR4/CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev. 29:709–722. 2010. View Article : Google Scholar : PubMed/NCBI
21	Hong X, Jiang F, Kalkanis SN, Zhang ZG, Zhang XP, DeCarvalho AC, Katakowski M, Bobbitt K, Mikkelsen T and Chopp M: SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion. Cancer Lett. 236:39–45. 2006. View Article : Google Scholar : PubMed/NCBI
22	Lu DY, Tang CH, Yeh WL, Wong KL, Lin CP, Chen YH, Lai CH, Chen YF, Leung YM and Fu WM: SDF-1alpha up-regulates interleukin-6 through CXCR4, PI3K/Akt, ERK, and NF-kappaB-dependent pathway in microglia. Eur J Pharmacol. 613:146–154. 2009. View Article : Google Scholar : PubMed/NCBI
23	Kryczek I, Lange A, Mottram P, Alvarez X, Cheng P, Hogan M, Moons L, Wei S, Zou L, Machelon V, et al: CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res. 65:465–472. 2005.PubMed/NCBI
24	Mirshahi F, Pourtau J, Li H, Muraine M, Trochon V, Legrand E, Vannier J, Soria J, Vasse M and Soria C: SDF-1 activity on microvascular endothelial cells: Consequences on angiogenesis in in vitro and in vivo models. Thromb Res. 99:587–594. 2000. View Article : Google Scholar : PubMed/NCBI
25	Guleng B, Tateishi K, Ohta M, Kanai F, Jazag A, Ijichi H, Tanaka Y, Washida M, Morikane K, Fukushima Y, et al: Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res. 65:5864–5871. 2005. View Article : Google Scholar : PubMed/NCBI
26	Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S, et al: The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature. 393:591–594. 1998. View Article : Google Scholar : PubMed/NCBI
27	Lv S, Sun B, Zhong X, Dai C, Wang W, Ma X, Song H, Shi R and Wang R: The clinical implications of chemokine receptor CXCR4 in grade and prognosis of glioma patients: A meta-analysis. Mol Neurobiol. 52:555–561. 2015. View Article : Google Scholar : PubMed/NCBI