Multivoxel Magnetic Resonance Spectroscopy Identifies Enriched Foci of Cancer Stem-like Cells in High-grade Gliomas

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2017 Jan 25

PMID 28115854

Citations 3

Authors

Tao He

Tianming Qiu

Xiaodong Wang

Hongxing Gui

Xilong Wang

Qikuan Hu

Hechun Xia

Gaoyang Qi

Jinsong Wu

Hui Ma

Affiliations

Soon will be listed here.

Abstract

Objective: This study investigated the correlation between choline/creatine (Cho/Cr) ratios determined by multivoxel proton magnetic resonance spectroscopy (H-MRS) and the distribution of cancer stem-like cells (CSLCs) in high-grade gliomas.

Patients And Methods: Sixteen patients with high-grade gliomas were recruited and underwent H-MRS examination before surgery to identify distinct tumor regions with variable Cho/Cr ratios. Using intraoperative neuronavigation, tumor tissues were accurately sampled from regions with high and low Cho/Cr ratios within each tumor. The distribution of CSLCs in samples from glioma tissue regions with different Cho/Cr ratios was quantified by neurosphere culture, immunohistochemistry, and Western blot.

Results: The mean neurosphere formation rate in tissues with high Cho/Cr ratios was significantly increased compared with that in low Cho/Cr ratio tissues (13.94±5.94 per 100 cells vs 8.04±3.99 per 100 cells, <0.001). Immunohistochemistry indicated that tissues with high Cho/Cr ratios had elevated expression of CD133, nestin, and CD15, relative to low Cho/Cr ratio tissue samples (23.6%±3.8% vs 18.3%±3.3%, 25.2%±4.5% vs 19.8%±2.8%, 24.5%±3.8% vs 17.8%±2.2%, respectively; all <0.001). Western blot demonstrated that relative CD133 and nestin protein expression in high Cho/Cr ratio regions was significantly higher than that in low Cho/Cr ratio tissue samples (0.50±0.17 vs 0.30±0.08, 0.45±0.13 vs 0.27±0.07, respectively; both <0.001). The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (=0.897 and =0.861, respectively).

Conclusion: Cho/Cr ratios correlate with the distribution of CSLCs in high-grade gliomas, and this may assist in identifying foci enriched with CSLCs and thus improve the management of high-grade gliomas.

Citing Articles

Advanced magnetic resonance spectroscopic neuroimaging: Experts' consensus recommendations.

Maudsley A, Andronesi O, Barker P, Bizzi A, Bogner W, Henning A NMR Biomed. 2020; 34(5):e4309.

PMID: 32350978 PMC: 7606742. DOI: 10.1002/nbm.4309.

Multivoxel H-MR Spectroscopy Biometrics for Preoprerative Differentiation Between Brain Tumors.

Durmo F, Rydelius A, Cuellar Baena S, Askaner K, Latt J, Bengzon J Tomography. 2018; 4(4):172-181.

PMID: 30588503 PMC: 6299741. DOI: 10.18383/j.tom.2018.00051.

The biology and mathematical modelling of glioma invasion: a review.

Alfonso J, Talkenberger K, Seifert M, Klink B, Hawkins-Daarud A, Swanson K J R Soc Interface. 2017; 14(136).

PMID: 29118112 PMC: 5721156. DOI: 10.1098/rsif.2017.0490.

References

Bruhn H, Frahm J, Gyngell M, Merboldt K, Hanicke W, Sauter R . Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors. Radiology. 1989; 172(2):541-8. DOI: 10.1148/radiology.172.2.2748837. View

Caro P, Kishan A, Norberg E, Stanley I, Chapuy B, Ficarro S . Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell. 2012; 22(4):547-60. PMC: 3479446. DOI: 10.1016/j.ccr.2012.08.014. View

Chen J, Li Y, Yu T, McKay R, Burns D, Kernie S . A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012; 488(7412):522-6. PMC: 3427400. DOI: 10.1038/nature11287. View

Zhang J, Zhuang D, Yao C, Lin C, Wang T, Qin Z . Metabolic approach for tumor delineation in glioma surgery: 3D MR spectroscopy image-guided resection. J Neurosurg. 2015; 124(6):1585-93. DOI: 10.3171/2015.6.JNS142651. View

Ignatova T, Kukekov V, Laywell E, Suslov O, Vrionis F, Steindler D . Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia. 2002; 39(3):193-206. DOI: 10.1002/glia.10094. View

Bloch O, Han S, Cha S, Sun M, Aghi M, McDermott M . Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg. 2012; 117(6):1032-8. DOI: 10.3171/2012.9.JNS12504. View

Verma A, Kumar I, Verma N, Aggarwal P, Ojha R . Magnetic resonance spectroscopy - Revisiting the biochemical and molecular milieu of brain tumors. BBA Clin. 2016; 5:170-8. PMC: 4845155. DOI: 10.1016/j.bbacli.2016.04.002. View

Niculescu M, Zeisel S . Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr. 2002; 132(8 Suppl):2333S-2335S. DOI: 10.1093/jn/132.8.2333S. View

Glunde K, Bhujwalla Z, Ronen S . Choline metabolism in malignant transformation. Nat Rev Cancer. 2011; 11(12):835-48. PMC: 4337883. DOI: 10.1038/nrc3162. View

10.

Wang Q, Zhang H, Zhang J, Wu C, Zhu W, Li F . The diagnostic performance of magnetic resonance spectroscopy in differentiating high-from low-grade gliomas: A systematic review and meta-analysis. Eur Radiol. 2015; 26(8):2670-84. DOI: 10.1007/s00330-015-4046-z. View

11.

McKnight T, Lamborn K, Love T, Berger M, Chang S, Dillon W . Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas. J Neurosurg. 2007; 106(4):660-6. DOI: 10.3171/jns.2007.106.4.660. View

12.

Fink J, Carr R, Matsusue E, Iyer R, Rockhill J, Haynor D . Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from posttreatment effects. J Magn Reson Imaging. 2011; 35(1):56-63. DOI: 10.1002/jmri.22801. View

13.

Clark P, Mai W, Cloughesy T, Nathanson D . Emerging Approaches for Targeting Metabolic Vulnerabilities in Malignant Glioma. Curr Neurol Neurosci Rep. 2016; 16(2):17. DOI: 10.1007/s11910-015-0613-6. View

14.

Terunuma A, Putluri N, Mishra P, Mathe E, Dorsey T, Yi M . MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Invest. 2013; 124(1):398-412. PMC: 3871244. DOI: 10.1172/JCI71180. View

15.

Lin A, Ross B, Harris K, Wong W . Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. NeuroRx. 2005; 2(2):197-214. PMC: 1064986. DOI: 10.1602/neurorx.2.2.197. View

16.

Brescia P, Richichi C, Pelicci G . Current strategies for identification of glioma stem cells: adequate or unsatisfactory?. J Oncol. 2012; 2012:376894. PMC: 3366252. DOI: 10.1155/2012/376894. View

17.

Zeng Q, Liu H, Zhang K, Li C, Zhou G . Noninvasive evaluation of cerebral glioma grade by using multivoxel 3D proton MR spectroscopy. Magn Reson Imaging. 2010; 29(1):25-31. DOI: 10.1016/j.mri.2010.07.017. View

18.

Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z . Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res. 2008; 27:85. PMC: 2633002. DOI: 10.1186/1756-9966-27-85. View

19.

Hensley C, Faubert B, Yuan Q, Lev-Cohain N, Jin E, Kim J . Metabolic Heterogeneity in Human Lung Tumors. Cell. 2016; 164(4):681-94. PMC: 4752889. DOI: 10.1016/j.cell.2015.12.034. View

20.

Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A . The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2):97-109. PMC: 1929165. DOI: 10.1007/s00401-007-0243-4. View