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

Overview

Journal Neurosurgery

Specialty Neurosurgery

Date 2008 Sep 25

PMID 18812968

Citations 33

Authors

Charles B Stevenson

Moneeb Ehtesham

Kathryn M McMillan

J Gerardo Valadez

Michael L Edgeworth

Ronald R Price

Ty W Abel

Khubaib Y Mapara

Reid C Thompson

Affiliations

Soon will be listed here.

Abstract

Objective: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process.

Methods: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain.

Results: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas.

Conclusion: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

Citing Articles

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme: a systematic review going beyond pathologic implications.

Vageli D, Doukas P, Goupou K, Benos A, Astara K, Zacharouli K Oncol Res. 2024; 32(8):1239-1256.

PMID: 39055895 PMC: 11267112. DOI: 10.32604/or.2024.052130.

Supramaximal resection: retrospective study on IDH-wildtype Glioblastomas based on the new RANO-Resect classification.

Tropeano M, Raspagliesi L, Bono B, Baram A, Rossini Z, Franzini A Acta Neurochir (Wien). 2024; 166(1):196.

PMID: 38676720 DOI: 10.1007/s00701-024-06090-2.

Neuroinflammation in Glioblastoma: The Role of the Microenvironment in Tumour Progression.

Nobrega A, Pimentel R, Prado A, Garcia J, Frozza R, Bernardi A Curr Cancer Drug Targets. 2024; 24(6):579-594.

PMID: 38310461 DOI: 10.2174/0115680096265849231031101449.

Stem cell-nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy.

Lai Y, Su C, Cheng H, Chu C, Jeng L, Chiang C Nat Commun. 2023; 14(1):285.

PMID: 36650171 PMC: 9845336. DOI: 10.1038/s41467-023-35935-0.

Current Status of Ga-Pentixafor in Solid Tumours.

Hadebe B, Sathekge M, Aldous C, Vorster M Diagnostics (Basel). 2022; 12(9).

PMID: 36140541 PMC: 9497673. DOI: 10.3390/diagnostics12092135.

References

Zeelenberg I, Ruuls-Van Stalle L, Roos E . The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res. 2003; 63(13):3833-9. View

Rubin J, Kung A, Klein R, Chan J, Sun Y, Schmidt K . A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A. 2003; 100(23):13513-8. PMC: 263845. DOI: 10.1073/pnas.2235846100. View

Spano J, Andre F, Morat L, Sabatier L, Besse B, Combadiere C . Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome. Ann Oncol. 2004; 15(4):613-7. DOI: 10.1093/annonc/mdh136. View

Salmaggi A, Gelati M, Pollo B, Frigerio S, Eoli M, Silvani A . CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells. J Neurooncol. 2004; 67(3):305-17. DOI: 10.1023/b:neon.0000024241.05346.24. View

Kelly P, Daumas-Duport C, Kispert D, Kall B, Scheithauer B, Illig J . Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg. 1987; 66(6):865-74. DOI: 10.3171/jns.1987.66.6.0865. View

Hammoud M, Sawaya R, Shi W, Thall P, Leeds N . Prognostic significance of preoperative MRI scans in glioblastoma multiforme. J Neurooncol. 1996; 27(1):65-73. DOI: 10.1007/BF00146086. View

van Buchem M, McGOWAN J, Kolson D, Polansky M, Grossman R . Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden. Magn Reson Med. 1996; 36(4):632-6. DOI: 10.1002/mrm.1910360420. View

Ma Q, Jones D, Borghesani P, Segal R, Nagasawa T, Kishimoto T . Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A. 1998; 95(16):9448-53. PMC: 21358. DOI: 10.1073/pnas.95.16.9448. View

Nagashima G, Suzuki R, Hokaku H, Takahashi M, Miyo T, Asai J . Graphic analysis of microscopic tumor cell infiltration, proliferative potential, and vascular endothelial growth factor expression in an autopsy brain with glioblastoma. Surg Neurol. 1999; 51(3):292-9. DOI: 10.1016/s0090-3019(98)00056-1. View

10.

Laverdiere C, Hoang B, Yang R, Sowers R, Qin J, Meyers P . Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. 2005; 11(7):2561-7. DOI: 10.1158/1078-0432.CCR-04-1089. View

11.

Kim J, Takeuchi H, Lam S, Turner R, Wang H, Kuo C . Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005; 23(12):2744-53. DOI: 10.1200/JCO.2005.07.078. View

12.

Ohgaki H, Kleihues P . Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005; 64(6):479-89. DOI: 10.1093/jnen/64.6.479. View

13.

Saur D, Seidler B, Schneider G, Algul H, Beck R, Senekowitsch-Schmidtke R . CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology. 2005; 129(4):1237-50. DOI: 10.1053/j.gastro.2005.06.056. View

14.

Pope W, Sayre J, Perlina A, Villablanca J, Mischel P, Cloughesy T . MR imaging correlates of survival in patients with high-grade gliomas. AJNR Am J Neuroradiol. 2005; 26(10):2466-74. PMC: 7976216. View

15.

Su L, Zhang J, Xu H, Wang Y, Chu Y, Liu R . Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells. Clin Cancer Res. 2005; 11(23):8273-80. DOI: 10.1158/1078-0432.CCR-05-0537. View

16.

Odemis V, Lamp E, Pezeshki G, Moepps B, Schilling K, Gierschik P . Mice deficient in the chemokine receptor CXCR4 exhibit impaired limb innervation and myogenesis. Mol Cell Neurosci. 2005; 30(4):494-505. DOI: 10.1016/j.mcn.2005.07.019. View

17.

Aghi M, Gaviani P, Henson J, Batchelor T, Louis D, Barker 2nd F . Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma. Clin Cancer Res. 2005; 11(24 Pt 1):8600-5. DOI: 10.1158/1078-0432.CCR-05-0713. View

18.

Yamamoto A, Miki Y, Adachi S, Kanagaki M, Fushimi Y, Okada T . Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy. Eur J Radiol. 2005; 57(3):423-7. DOI: 10.1016/j.ejrad.2005.09.008. View

19.

Ehtesham M, Winston J, Kabos P, Thompson R . CXCR4 expression mediates glioma cell invasiveness. Oncogene. 2006; 25(19):2801-6. DOI: 10.1038/sj.onc.1209302. View

20.

Engl T, Relja B, Marian D, Blumenberg C, Muller I, Beecken W . CXCR4 chemokine receptor mediates prostate tumor cell adhesion through alpha5 and beta3 integrins. Neoplasia. 2006; 8(4):290-301. PMC: 1600676. DOI: 10.1593/neo.05694. View