DOI QR코드

DOI QR Code

Expression of Chemokines and Chemokine Receptors in Brain Tumor Tissue Derived Cells

  • Razmkhah, Mahboobeh (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Arabpour, Fahimeh (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Taghipour, Mousa (Department of Neurosurgery, School of Medicine, Shiraz University of Medical Sciences) ;
  • Mehrafshan, Ali (Department of Neurosurgery, School of Medicine, Shiraz University of Medical Sciences) ;
  • Chenari, Nooshafarin (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Ghaderi, Abbas (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences)
  • Published : 2014.09.15

Abstract

Chemokine and chemokine receptor expression by tumor cells contributes to tumor growth and angiogenesis and thus these factors may be considered as tumor markers. Here we aimed to characterize cells directly extracted from glioma, meningioma, and secondary brain tumors as well as non-tumoral cells in vitro. Cells were isolated from brain tissues using 0.2% collagenase and characterized by flow cytometry. Expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, MCP-1 and IP-10 was defined using flow cytometry and qRT-PCR methods. Brain tissue isolated cells were observed as spindle-shaped cell populations. No significant differences were observed for expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, and IP-10 transcripts. However, the expression of CXCR4 was approximately 13-fold and 110-fold higher than its counterpart, CXCR7, in meningioma and glioma cells, respectively. CXCR7 was not detectable in secondary tumors but CXCR4 was expressed. In non tumoral cells, CXCR7 had 1.3-fold higher mRNA expression than CXCR4. Flow cytometry analyses of RANTES, MCP-1, IP-10, CCR5 and CXCR4 expression showed no significant difference between low and high grade gliomas. Differential expression of CXCR4 and CXCR7 in brain tumors derived cells compared to non-tumoral samples may have crucial impacts on therapeutic interventions targeting the SDF-1/CXCR4/CXCR7 axis.

Keywords

Brain tumors;chemokine;chemokine receptor;meningioma;glioma

Acknowledgement

Supported by : Shiraz University of Medical Sciences, Shiraz Institute for Cancer Research

References

  1. Albulescu R, Codrici E, Popescu ID, et al (2013). Cytokine patterns in brain tumour progression. Mediators Inflamm, 2013, 979748.
  2. Bajetto A, Barbieri F, Pattarozzi A, et al (2007). CXCR4 and SDF1 expression in human meningiomas: a proliferative role in tumoral meningothelial cells in vitro. Neuro Oncol, 9, 3-11.
  3. Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G (2001). Chemokines and their receptors in the central nervous system. Front Neuroendocrinol, 22, 147-84. https://doi.org/10.1006/frne.2001.0214
  4. Barbieri F, Bajetto A, Porcile C, et al (2006). CXC receptor and chemokine expression in human meningioma: SDF1/CXCR4 signaling activates ERK1/2 and stimulates meningioma cell proliferation. Ann N Y Acad Sci, 1090, 332-43. https://doi.org/10.1196/annals.1378.037
  5. Bian XW, Yang SX, Chen JH, et al (2007). Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival. Neurosurgery, 61, 570-8. https://doi.org/10.1227/01.NEU.0000290905.53685.A2
  6. Brewer GJ and LeRoux PD (2007). Human primary brain tumor cell growth inhibition in serum-free medium optimized for neuron survival. Brain Res, 1157, 156-66. https://doi.org/10.1016/j.brainres.2007.04.064
  7. Domanska UM, Kruizinga RC, den Dunnen WF, et al (2011). The chemokine network, a newly discovered target in high grade gliomas. Crit Rev Oncol Hematol, 79, 154-63. https://doi.org/10.1016/j.critrevonc.2010.07.006
  8. Dwyer J, Hebda JK, Le Guelte A, et al (2012). Glioblastoma cell-secreted interleukin-8 induces brain endothelial cell permeability via CXCR2. PLoS One, 7, 45562. https://doi.org/10.1371/journal.pone.0045562
  9. Ehtesham M, Winston JA, Kabos P, Thompson RC (2006). CXCR4 expression mediates glioma cell invasiveness. Oncogene, 25, 2801-6. https://doi.org/10.1038/sj.onc.1209302
  10. Hattermann K, Held-Feindt J, Lucius R, et al (2010). The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res, 70, 3299-308. https://doi.org/10.1158/0008-5472.CAN-09-3642
  11. Komatani H, Sugita Y, Arakawa F, Ohshima K, Shigemori M (2009). Expression of CXCL12 on pseudopalisading cells and proliferating microvessels in glioblastomas: an accelerated growth factor in glioblastomas. Int J Oncol, 34, 665-72.
  12. Lee S, Jilani S, Nikolova GV, Carpizo D, Iruela-Arispe ML (2005). Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol, 169, 681-91. https://doi.org/10.1083/jcb.200409115
  13. Leung SY, Wong MP, Chung LP, Chan AS, Yuen ST (1997). Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas. Acta Neuropathol, 93, 518-27. https://doi.org/10.1007/s004010050647
  14. Liberman J, Sartelet H, Flahaut M, et al (2012). Involvement of the CXCR7/CXCR4/CXCL12 axis in the malignant progression of human neuroblastoma. PLoS One, 7, 43665. https://doi.org/10.1371/journal.pone.0043665
  15. Liu G, Yuan X, Zeng Z, et al (2006). Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer, 5, 61. https://doi.org/10.1186/1476-4598-5-61
  16. Ludwig A, Schulte A, Schnack C, et al (2005). Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells. J Neurochem, 93, 1293-303. https://doi.org/10.1111/j.1471-4159.2005.03123.x
  17. Madden SL, Cook BP, Nacht M, et al (2004). Vascular gene expression in nonneoplastic and malignant brain. Am J Pathol, 165, 601-8. https://doi.org/10.1016/S0002-9440(10)63324-X
  18. Maru SV, Holloway KA, Flynn G, et al (2008). Chemokine production and chemokine receptor expression by human glioma cells: role of CXCL10 in tumour cell proliferation. J Neuroimmunol, 199, 35-45. https://doi.org/10.1016/j.jneuroim.2008.04.029
  19. Nakahata AM, Suzuki DE, Rodini CO, et al (2010). Human glioblastoma cells display mesenchymal stem cell features and form intracranial tumors in immunocompetent rats. J Stem Cells, 5, 103-11.
  20. Nishie A, Ono M, Shono T, et al (1999). Macrophage infiltration and hemeoxygenase-1 expression correlate with angiogenesis in human gliomas. Clin Cancer Res, 5, 1107-13.
  21. Oh JW, Drabik K, Kutsch O, et al (2001). CXC chemokine receptor 4 expression and function in human astroglioma cells. J Immunol, 166, 2695-704. https://doi.org/10.4049/jimmunol.166.4.2695
  22. Rempel SA, Dudas S, Ge S, Gutierrez JA (2000). Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res, 6, 102-11.
  23. Sciume G, Santoni A, Bernardini G (2010). Chemokines and glioma: invasion and more. J Neuroimmunol, 224, 8-12. https://doi.org/10.1016/j.jneuroim.2010.05.019
  24. Stevenson CB, Ehtesham M, McMillan KM, et al (2008). 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, 560-9. https://doi.org/10.1227/01.NEU.0000324896.26088.EF
  25. Tang T, Xia QJ, Chen JB, Xi MR, Lei D (2012). Expression of the CXCL12/SDF-1 chemokine receptor CXCR7 in human brain tumours. Asian Pac J Cancer Prev, 13, 5281-6. https://doi.org/10.7314/APJCP.2012.13.10.5281
  26. Teicher BA and Fricker SP (2010). CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res, 16, 2927-31.
  27. Wang SC, Hong JH, Hsueh C, Chiang CS (2012). Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model. Lab Invest, 92, 151-62. https://doi.org/10.1038/labinvest.2011.128
  28. Wurth R, Barbieri F, Bajetto A, et al (2011). Expression of CXCR7 chemokine receptor in human meningioma cells and in intratumoral microvasculature. J Neuroimmunol, 234, 115-23. https://doi.org/10.1016/j.jneuroim.2011.01.006
  29. Yang YC, Lee ZY, Wu CC, et al (2007). CXCR4 expression is associated with pelvic lymph node metastasis in cervical adenocarcinoma. Int J Gynecol Cancer, 17, 676-86. https://doi.org/10.1111/j.1525-1438.2007.00841.x
  30. Zheng H, Fu G, Dai T, Huang H (2007). Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol, 50, 274-280. https://doi.org/10.1097/FJC.0b013e318093ec8f
  31. Zhou Y, Larsen PH, Hao C, Yong VW (2002). CXCR4 is a mayor chemokine receptor on glioma cells and mediates their survival. J Biol Chem, 277, 49481-7. https://doi.org/10.1074/jbc.M206222200

Cited by

  1. The human chemokine receptor CCRL2 suppresses chemotaxis and invasion by blocking CCL2-induced phosphorylation of p38 MAPK in human breast cancer cells vol.32, pp.11, 2015, https://doi.org/10.1007/s12032-015-0696-6
  2. Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas vol.48, pp.4, 2016, https://doi.org/10.3892/ijo.2016.3354
  3. Recent developments in targeted imaging of CXCR4-chemokine receptor vol.317, pp.1, 2018, https://doi.org/10.1007/s10967-018-5910-5
  4. Differential somatostatin, CXCR4 chemokine and endothelin A receptor expression in WHO grade I–IV astrocytic brain tumors vol.144, pp.7, 2018, https://doi.org/10.1007/s00432-018-2645-1