Response-predictive Gene Expression Profiling of Glioma Progenitor Cells in Vitro

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Oct 1

PMID 25268354

Citations 11

Authors

Sylvia Moeckel

Katharina Meyer

Petra Leukel

Fabian Heudorfer

Corinna Seliger

Christina Stangl

Ulrich Bogdahn

Martin Proescholdt

Alexander Brawanski

Arabel Vollmann-Zwerenz

Markus J Riemenschneider

Anja-Katrin Bosserhoff

Rainer Spang

Peter Hau

Affiliations

Soon will be listed here.

Abstract

Background: High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.

Methods: In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a) to enrich specimens for brain tumor initiating cells and (b) to confront cells with a therapeutic agent before expression profiling.

Results: As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.

Conclusion: For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

Citing Articles

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References

Chahal M, Xu Y, Lesniak D, Graham K, Famulski K, Christensen J . MGMT modulates glioblastoma angiogenesis and response to the tyrosine kinase inhibitor sunitinib. Neuro Oncol. 2010; 12(8):822-33. PMC: 2940678. DOI: 10.1093/neuonc/noq017. View

Irizarry R, Hobbs B, Collin F, Beazer-Barclay Y, Antonellis K, Scherf U . Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2):249-64. DOI: 10.1093/biostatistics/4.2.249. View

Friedl P, Gilmour D . Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009; 10(7):445-57. DOI: 10.1038/nrm2720. View

Pan E, Yu D, Yue B, Potthast L, Chowdhary S, Smith P . A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. J Neurooncol. 2012; 110(1):111-8. PMC: 5735835. DOI: 10.1007/s11060-012-0943-z. View

Singh S, Hawkins C, Clarke I, Squire J, Bayani J, Hide T . Identification of human brain tumour initiating cells. Nature. 2004; 432(7015):396-401. DOI: 10.1038/nature03128. View

Giannopoulou E, Dimitropoulos K, Argyriou A, Koutras A, Dimitrakopoulos F, Kalofonos H . An in vitro study, evaluating the effect of sunitinib and/or lapatinib on two glioma cell lines. Invest New Drugs. 2009; 28(5):554-60. DOI: 10.1007/s10637-009-9290-0. View

Deryugina E, Bourdon M . Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin. J Cell Sci. 1996; 109 ( Pt 3):643-52. DOI: 10.1242/jcs.109.3.643. View

Pardal R, Clarke M, Morrison S . Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2004; 3(12):895-902. DOI: 10.1038/nrc1232. View

Phillips H, Kharbanda S, Chen R, Forrest W, Soriano R, Wu T . Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006; 9(3):157-73. DOI: 10.1016/j.ccr.2006.02.019. View

10.

Wen P, Macdonald D, Reardon D, Cloughesy T, Sorensen A, Galanis E . Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010; 28(11):1963-72. DOI: 10.1200/JCO.2009.26.3541. View

11.

Nazarenko I, Hede S, He X, Hedren A, Thompson J, Lindstrom M . PDGF and PDGF receptors in glioma. Ups J Med Sci. 2012; 117(2):99-112. PMC: 3339542. DOI: 10.3109/03009734.2012.665097. View

12.

Stupp R, van den Bent M, Hegi M . Optimal role of temozolomide in the treatment of malignant gliomas. Curr Neurol Neurosci Rep. 2005; 5(3):198-206. DOI: 10.1007/s11910-005-0047-7. View

13.

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M . Long-term survival with glioblastoma multiforme. Brain. 2007; 130(Pt 10):2596-606. DOI: 10.1093/brain/awm204. View

14.

Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

15.

McCord A, Jamal M, Williams E, Camphausen K, Tofilon P . CD133+ glioblastoma stem-like cells are radiosensitive with a defective DNA damage response compared with established cell lines. Clin Cancer Res. 2009; 15(16):5145-53. PMC: 6290462. DOI: 10.1158/1078-0432.CCR-09-0263. View

16.

Gotink K, Broxterman H, Labots M, de Haas R, Dekker H, Honeywell R . Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res. 2011; 17(23):7337-46. PMC: 4461037. DOI: 10.1158/1078-0432.CCR-11-1667. View

17.

Neyns B, Sadones J, Chaskis C, Dujardin M, Everaert H, Lv S . Phase II study of sunitinib malate in patients with recurrent high-grade glioma. J Neurooncol. 2010; 103(3):491-501. DOI: 10.1007/s11060-010-0402-7. View

18.

Faivre S, Demetri G, Sargent W, Raymond E . Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov. 2007; 6(9):734-45. DOI: 10.1038/nrd2380. View

19.

Weller M, Stupp R, Hegi M, Wick W . Individualized targeted therapy for glioblastoma: fact or fiction?. Cancer J. 2012; 18(1):40-4. DOI: 10.1097/PPO.0b013e318243f6c9. View

20.

Nilsson M, Zage P, Zeng L, Xu L, Cascone T, Wu H . Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors. Oncogene. 2010; 29(20):2938-49. DOI: 10.1038/onc.2010.60. View