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Article

Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication

  • Authors:
    • Qingtang Lin
    • Zhao Liu
    • Feng Ling
    • Geng Xu
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100054, P.R. China
  • Pages: 1329-1335
    |
    Published online on: December 11, 2015
       https://doi.org/10.3892/mmr.2015.4680
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Abstract

Gliomas are the most common type of primary brain tumor. Using current standard treatment regimens, the prognosis of patients with gliomas remains poor, which is predominantly due to the resistance of glioma cells to chemotherapy. The organ microenvironment has been implicated in the pathogenesis and survival of tumor cells. Thus, the aim of the present study was to test the hypothesis that astrocytes (the housekeeping cells of the brain microenvironment) may protect glioma cells from chemotherapy and to investigate the underlying mechanism. Immunofluorescent and scanning electron microscopy demonstrated that glioma cells were surrounded and infiltrated by activated astrocytes. In vitro co‑culture of glioma cells with astrocytes significantly reduced the cytotoxic effects on glioma cells caused by various chemotherapeutic agents, as demonstrated by fluorescein isothiocyanate‑propidium iodide flow cytometry. Transwell experiments indicated that this protective effect was dependent on physical contact and the gap junctional communication (GJC) between astrocytes and glioma cells. Microarray expression profiling further revealed that astrocytes upregulated the expression levels of various critical survival genes in the glioma cells via GJC. The results of the present study indicated that the organ microenvironment may affect the biological behavior of tumor cells and suggest a novel mechanism of resistance in glioma cells, which may be of therapeutic relevance clinically.
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1 

Wrensch M, Minn Y, Chew T, Bondy M and Berger MS: Epidemiology of primary brain tumors: Current concepts and review of the literature. Neuro Oncol. 4:278–299. 2002.PubMed/NCBI

2 

Fisher JL, Schwartzbaum JA, Wrensch M and Wiemels JL: Epidemiology of brain tumors. Neurol Clin. 25:867–890. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Lévy S, Chapet S and Mazeron JJ: Management of gliomas. Cancer Radiother. 18:461–467. 2014. View Article : Google Scholar

4 

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Ashmore SM, Thomas DG and Darling JL: Does P-glycoprotein play a role in clinical resistance of malignant astrocytoma? Anticancer Drugs. 10:861–872. 1999. View Article : Google Scholar

6 

Jennings MT and Iyengar S: The molecular genetics of therapeutic resistance in malignant astrocytomas. Am J Pharmacogenomics. 1:93–99. 2001. View Article : Google Scholar

7 

Shapiro WR and Shapiro JR: Principles of brain tumor chemotherapy. Semin Oncol. 13:56–69. 1986.PubMed/NCBI

8 

Mousseau M: Chemotherapy of brain tumors: Biological basis of its limited efficacy. Bull Cancer. 81:414–424. 1994.In French. PubMed/NCBI

9 

Stewart DJ: A critique of the role of the blood-brain barrier in the chemotherapy of human brain tumors. J Neurooncol. 20:121–139. 1994. View Article : Google Scholar : PubMed/NCBI

10 

Zhang RD, Price JE, Fujimaki T, Bucana CD and Fidler IJ: Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am J Pathol. 141:1115–1124. 1992.PubMed/NCBI

11 

Hoelzinger DB, Demuth T and Berens ME: Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst. 99:1583–1593. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Fidler IJ: The pathogenesis of cancer metastasis: The 'seed and soil' hypothesis revisited. Nat Rev Cancer. 3:453–458. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Abbott NJ, Rönnbäck L and Hansson E: Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 7:41–53. 2006. View Article : Google Scholar

14 

Fields RD and Stevens-Graham B: New insights into neuron-glia communication. Science. 298:556–562. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Bullock TH, Bennett MV, Johnston D, Josephson R, Marder E and Fields RD: Neuroscience: The neuron doctrine, redux. Science. 310:791–793. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Miller G: Neuroscience: The dark side of glia. Science. 308:778–781. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Allen NJ and Barres BA: Neuroscience: Glia-more than just brain glue. Nature. 457:675–677. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Sofroniew MV: Reactive astrocytes in neural repair and protection. Neuroscientist. 11:400–407. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Crooks DA, Scholtz CL, Vowles G, Greenwald S and Evans S: The glial reaction in closed head injuries. Neuropathol Appl Neurobiol. 17:407–411. 1991. View Article : Google Scholar : PubMed/NCBI

20 

Mahesh VB, Dhandapani KM and Brann DW: Role of astrocytes in reproduction and neuroprotection. Mol Cell Endocrinol. 246:1–9. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Chen LW, Yung KL and Chan YS: Reactive astrocytes as potential manipulation targets in novel cell replacement therapy of Parkinson's disease. Curr Drug Targets. 6:821–833. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Krysko DV, Leybaert L, Vandenabeele P and D'Herde K: Gap junctions and the propagation of cell survival and cell death signals. Apoptosis. 10:459–469. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Lin JH, Weigel H, Cotrina ML, Liu S, Bueno E, Hansen AJ, Hansen TW, Goldman S and Nedergaard M: Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci. 1:494–500. 1998. View Article : Google Scholar

24 

Rouach N, Avignone E, Même W, Koulakoff A, Venance L, Blomstrand F and Giaume C: Gap junctions and connexin expression in the normal and pathological central nervous system. Biol Cell. 94:457–475. 2002. View Article : Google Scholar

25 

Zhang W, Couldwell WT, Simard MF, Song H, Lin JH and Nedergaard M: Direct gap junction communication between malignant glioma cells and astrocytes. Cancer Res. 59:1994–2003. 1999.PubMed/NCBI

26 

Zhou B, Bu G, Zhou Y, Zhao Y, Li W and Li M: Knockdown of CDC2 expression inhibits proliferation, enhances apoptosis and increases chemosensitivity to temozolomide in glioblastoma cells. Med Oncol. 32:3782015. View Article : Google Scholar

27 

Chai KM, Wang CY, Liaw HJ, Fang KM, Yang CS and Tzeng SF: Downregulation of BRCA1-BRCA2-containing complex subunit 3 sensitizes glioma cells to temozolomide. Oncotarget. 5:10901–10915. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Langley RR, Fan D, Guo L, Zhang C, Lin Q, Brantley EC, McCarty JH and Fidler IJ: Generation of an immortalized astrocyte cell line from H-2Kb-tsA58 mice to study the role of astrocytes in brain metastasis. Int J Oncol. 35:665–672. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Grossman R, Brastianos H, Blakeley JO, Mangraviti A, Lal B, Zadnik P, Hwang L, Wicks RT, Goodwin RC, Brem H and Tyler B: Combination of anti-VEGF therapy and temozolomide in two experimental human glioma models. J Neurooncol. 116:59–65. 2014. View Article : Google Scholar :

30 

Peng Q, Moan J, Ma LW and Nesland JM: Uptake, localization and photodynamic effect of meso-tetra (hydroxyphenyl) porphine and its corresponding chlorin in normal and tumor tissues of mice bearing mammary carcinoma. Cancer Res. 55:2620–2626. 1995.PubMed/NCBI

31 

Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ and Hung MC: Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 13:385–393. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Bolstad BM, Irizarry RA, Astrand M and Speed TP: A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 19:185–193. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Hinkerohe D, Wolfkühler D, Haghikia A, Meier C, Faustmann PM and Schlegel U: Dexamethasone differentially regulates functional membrane properties in glioma cell lines and primary astrocytes in vitro. J Neurooncol. 103:479–489. 2011. View Article : Google Scholar

34 

Zhang B, Feng X, Wang J, Xu X, Liu H and Lin N: Adenovirus-mediated delivery of bFGF small interfering RNA increases levels of connexin 43 in the glioma cell line, U251. J Exp Clin Cancer Res. 29:32010. View Article : Google Scholar : PubMed/NCBI

35 

Goldberg GS, Moreno AP, Bechberger JF, Hearn SS, Shivers RR, MacPhee DJ, Zhang YC and Naus CC: Evidence that disruption of connexin particle arrangements in gap junction plaques is associated with inhibition of gap junctional communication by a glycyrrhetinic acid derivative. Exp Cell Res. 222:48–53. 1996. View Article : Google Scholar : PubMed/NCBI

36 

Guan X, Wilson S, Schlender KK and Ruch RJ: Gap-junction disassembly and connexin 43 dephosphorylation induced by 18 beta-glycyrrhetinic acid. Mol Carcinog. 16:157–164. 1996. View Article : Google Scholar : PubMed/NCBI

37 

Fidler IJ, Balasubramanian K, Lin Q, Kim SW and Kim SJ: The brain microenvironment and cancer metastasis. Mol Cells. 30:93–98. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lin Q, Liu Z, Ling F and Xu G: Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication. Mol Med Rep 13: 1329-1335, 2016.
APA
Lin, Q., Liu, Z., Ling, F., & Xu, G. (2016). Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication. Molecular Medicine Reports, 13, 1329-1335. https://doi.org/10.3892/mmr.2015.4680
MLA
Lin, Q., Liu, Z., Ling, F., Xu, G."Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication". Molecular Medicine Reports 13.2 (2016): 1329-1335.
Chicago
Lin, Q., Liu, Z., Ling, F., Xu, G."Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication". Molecular Medicine Reports 13, no. 2 (2016): 1329-1335. https://doi.org/10.3892/mmr.2015.4680
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Q, Liu Z, Ling F and Xu G: Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication. Mol Med Rep 13: 1329-1335, 2016.
APA
Lin, Q., Liu, Z., Ling, F., & Xu, G. (2016). Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication. Molecular Medicine Reports, 13, 1329-1335. https://doi.org/10.3892/mmr.2015.4680
MLA
Lin, Q., Liu, Z., Ling, F., Xu, G."Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication". Molecular Medicine Reports 13.2 (2016): 1329-1335.
Chicago
Lin, Q., Liu, Z., Ling, F., Xu, G."Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication". Molecular Medicine Reports 13, no. 2 (2016): 1329-1335. https://doi.org/10.3892/mmr.2015.4680
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