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Induction of matrix metalloproteinase-1 and glioma cell motility by nitric oxide

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

High grade gliomas invariably recur due in a large part to tumor cells permeating normal brain in an inaccessible, diffuse manner. Previous work demonstrates that the expression of matrix metalloproteinases (MMP) contributes to this characteristic. Not only can MMPs assist a cell in traversing its environment by clearing extracellular matrix molecules, but they can also impact non-traditional downstream signals that affect a cell’s ability to interact and respond to its surroundings. Contributions to the induction of MMP expression and functional significance in glioma are still under investigation. Evidence in other cancer settings indicates that nitric oxide (NO) may play a role in tumor/cell progression that can influence MMP production. Matrix metalloproteinase-1 (MMP-1), also known as interstitial collagenase, and the constitutive nitric oxide synthases (NOS) have been shown to be over-expressed in high grade gliomas. In the current study we investigated the potential involvements of NO with regard to MMP-1 and functional glioma cell movement. With the treatment of the NO donor sodium nitroprusside (SNP), there was significant induction of MMP-1 mRNA, secreted MMP-1 protein and motility of glioma cell lines within 48 h. RNA inhibition of MMP-1 through transient transfection of three MMP-1 specific siRNAs revealed a marked abrogation of the NO-mediated induction of motility. In addition, application of the NOS inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) impaired movement of glioma cells. These data provide evidence for a regulatory axis of high grade glioma cell movement from NO through MMP-1, with NOS inhibitor results showing promise for future pharmacologic investigation.

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References

  1. Buckner JC, Brown PD, O’Neil BP, Meyer FB, Wetmore CJ, Uhm JH (2007) Central nervous system tumors. Mayo Clin Proc 82:1271–1286

    Article  PubMed  Google Scholar 

  2. McKinney PA (2004) Brain tumors: incidence, survival, and aetiology. J Neurol Neurosurg Psychiatry 75((Suppl. 2)):12–17

    Google Scholar 

  3. Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL (2007) Epidemiology of brain tumors. Neurol Clin 25:867–890

    Article  PubMed  Google Scholar 

  4. Krex D, Klink B, Hartmann C et al (2007) Long-term survival with glioblastoma multiforme. Brain 130:2596–2606

    Article  PubMed  Google Scholar 

  5. Louis DN, Pomeroy SL, Cairncross JG (2002) Focus on central nervous system neoplasia. Cancer Cell 1:125–128

    Article  CAS  PubMed  Google Scholar 

  6. Lam-Himlin D, Espey MG, Perry G, Smith MA, Castellani RJ (2006) Malignant glioma progression and nitric oxide. Neurochem Int 49:764–768

    Article  CAS  PubMed  Google Scholar 

  7. VanMeter TE, Rooprai HK, Kibble MM, Fillmore HL, Broaddus WC, Pilkington GJ (2001) The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol 53:213–235

    Article  CAS  PubMed  Google Scholar 

  8. Fillmore HL, VanMeter TE, Broaddus WC (2001) Membrane-type metalloproteinases (MT-MMPs): expression and function during glioma invasion. J Neurooncol 53:187–202

    Article  CAS  PubMed  Google Scholar 

  9. Nakano A, Tani E, Miyazaki K, Yamamoto Y, Furuyama J (1995) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83(2):298–307

    Article  CAS  PubMed  Google Scholar 

  10. Stojic J, Hagemann C, Haas S et al (2008) Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas. Neurosci Res 60(1):40–49

    Article  CAS  PubMed  Google Scholar 

  11. McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13:534–540

    Article  CAS  PubMed  Google Scholar 

  12. McCready J, Broaddus WC, Sykes V, Fillmore HL (2005) Association of a single nucleotide polymorphism in the matrix metalloproteinase-1 promoter with glioblastoma. Int J Cancer 117:781–785

    Article  CAS  PubMed  Google Scholar 

  13. Yoshida M, Sagawa N, Itoh H et al (2001) Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells. Mol Hum Reprod 7:979–985

    Article  CAS  PubMed  Google Scholar 

  14. Choe T, Lee B, Park I, Hong S (2003) Inhibition of matrix metalloproteinase-1 and -2 expression using nitric oxide synthase inhibitors in UV-irradiated human dermal fibroblasts. J Cosmet Sci 54:229–238

    CAS  PubMed  Google Scholar 

  15. Ishii Y, Ogura T, Tatemichi M, Fujisawa H, Otsuka F, Esumi H (2002) Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines. Int J Cancer 103:161–168

    Article  Google Scholar 

  16. Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727–730

    CAS  PubMed  Google Scholar 

  17. Kao CL, Chiou SH, Chen HS et al (2003) Elevated nitric oxide levels in childhood brain tumors. Childs Nerv Syst 19:744–749

    Article  PubMed  Google Scholar 

  18. Bakshi A, Nag TC, Wadhwa S, Mahapatra AK, Sarkar C (1998) The expression of nitric oxide synthases in human brain tumours and peritumoral areas. J Neurol Sci 155:196–203

    Article  CAS  PubMed  Google Scholar 

  19. Iwata S, Nakagawa K, Harada H, Oka Y, Kumon Y, Sakaki S (1999) Endothelial nitric oxide synthase expression in tumor vasculature is correlated with malignancy in human supratentorial astrocytic tumors. Neurosurgery 45:24–28

    Article  CAS  PubMed  Google Scholar 

  20. Ludwig HC, Feiz-Erfan I, Bockermann V, Behnke-Mursch J, Schallock K, Markakis E (2000) Expression of nitric oxide synthase (NOS I-III) by immunohistochemistry and DNA in situ hybridization. Correlation with macrophage presence, vascular endothelial growth factor (VEGF) and oedema volumetric data in 220 glioblastomas. Anticancer Res 20:299–304

    CAS  PubMed  Google Scholar 

  21. Ludwig HC, Ahkavan-Shigari R, Rausch S et al (2000) Oedema extension in cerebral metastasis and correlation with the expression of nitric oxide synthase isozymes (NOS I-III). Anticancer Res 20:305–310

    CAS  PubMed  Google Scholar 

  22. Erdamar S, Bagci P, Oz B, Dirican A (2006) Correlation of endothelial nitric oxide synthase and vascular endothelial growth factor expression with malignancy in patients with astrocytic tumors. J BUON 11:213–216

    CAS  PubMed  Google Scholar 

  23. Broholm H, Braendstrup O, Lauritzen M (2001) Nitric oxide synthase expression of oligodendrogliomas. Clin Neuropathol 20:233–238

    CAS  PubMed  Google Scholar 

  24. Broholm H, Rubin I, Kruse A et al (2003) Nitric oxide synthase expression and enzymatic activity in human brain tumors. Clin Neuropathol 22:273–281

    CAS  PubMed  Google Scholar 

  25. Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6:521–534

    Article  CAS  PubMed  Google Scholar 

  26. Ridnour LA, Thomas DD, Donzelli S et al (2006) The biphasic nature of nitric oxide responses in tumor biology. Antioxid Redox Signal 8:1329–1337

    Article  CAS  PubMed  Google Scholar 

  27. Ederli L, Reale L, Madeo L et al (2009) NO release by nitric oxide donors in vitro and in planta. Plant Physiol Biochem 47(1):42–48

    Article  CAS  PubMed  Google Scholar 

  28. Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3(2):193–197

    Article  CAS  PubMed  Google Scholar 

  29. Limb GA, Matter K, Murphy G et al (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166(5):1555–1563

    CAS  PubMed  Google Scholar 

  30. Hodgson JG, Yeh RF, Ray A et al. (2009) Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts. Neuro Oncol [Epub ahead of print]

  31. Lin YM, Jan HJ, Lee CC et al (2008) Dexamethasone reduced invasiveness of human malignant glioblastoma cells through a MAPK phosphatase-1 (MKP-1) dependent mechanism. Eur J Pharmacol 593:1–9

    Article  CAS  PubMed  Google Scholar 

  32. Wang F, Zhang R, Xia T et al (2007) Inhibitory effects of nitric oxide on invasion of human cancer cells. Cancer Lett 257(2):274–282

    Article  CAS  PubMed  Google Scholar 

  33. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol 7(2):134–153

    Article  CAS  PubMed  Google Scholar 

  34. Gu Z, Kaul M, Yan B et al (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297:1186–1190

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the Nucleic Acids Research Facilities of the Massey Cancer Center, VCU for their performance of the real time PCR assays. Funding for this work was provided by the Hord Fund of the MCV Foundation. We are also grateful for the continued support of Dr. Harold Young, Chairman, Department of Neurosurgery at VCUHS.

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Authors and Affiliations

  1. Department of Anatomy & Neurobiology, Virginia Commonwealth University, 1101 E. Marshall St, P.O. Box 980709, Richmond, VA, 23298-0709, USA

    Nicholas A. Pullen

  2. Department of Neurosurgery, Harold F. Young Neurosurgical Center, Virginia Commonwealth University and VCU Health Systems, 417 North 11th Street, 6th floor, P.O. Box 980631, Richmond, VA, 23298-0631, USA

    Helen L. Fillmore

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  1. Nicholas A. Pullen
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Correspondence to Helen L. Fillmore.

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Pullen, N.A., Fillmore, H.L. Induction of matrix metalloproteinase-1 and glioma cell motility by nitric oxide. J Neurooncol 96, 201–209 (2010). https://doi.org/10.1007/s11060-009-9965-6

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  • DOI: https://doi.org/10.1007/s11060-009-9965-6

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