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Fotoohi, M., Hadi, N., & Namazi, F. (2019). Effect of Foretinib on Matrix Metalloproteinase-2 (MMP2) Expression in Glioblastoma. Research in Molecular Medicine (RMM), 6(4), 20–27. https://doi.org/10.18502/rmm.v6i4.4800
https://doi.org/10.18502/rmm.v6i4.4800
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Maryam Fotoohi
Maryam Fotoohi
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
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Nasrin Hadi
Nasrin Hadi
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
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Faezeh Namazi
Faezeh Namazi
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
Published Date
- Jul 14, 2019
Effect of Foretinib on Matrix Metalloproteinase-2 (MMP2) Expression in Glioblastoma
Abstract
Background: The most malignant form of infiltrating astrocytoma, glioblastoma multiforme (GBM), is one of the most aggressive human cancers. Foretinib diminished GBM cell invasion by downregulating the expression of matrix metalloproteinase 2 (MMP2).
Aim: The study aimed to examine the anti-tumor activity of foretinib and to test its effect on MMP2 expression in T98 cells.
Materials and Methods: T98 cells were used as an experimental model of glioblastoma. The effect of foretinib on the expression of MMP2 was evaluated using quantitative real-time polymerase chain reaction. Thereafter, the effect of foretinib on the enzyme levels of MMP was examined by zymography. Statistical analyses were performed with GraphPad Prism software.
Results: A reduction in the expression of MMP2 was observed with an increase in the concentration of foretinib.
Conclusion: Foretinib treatment leads to downregulation of MMP-2 and has a positive effect on T98 cells. We believe that foretinib can be subjected to further clinical investigation to develop a treatment for GBM.
References
[1] Haas-Kogan D, et al. Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr Biol. 1998:1195-S1.
[2] Ostrom QT, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15.suppl_2:ii1-ii56.
[3] Louis DN, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114.2:97-109.
[4] McKinley BP, et al. The impact of age and gender on the incidence of glial tumors in New York state from 1976–1995. J Neurosurg. 2000;93.6:932-939.
[5] Sloane D. Cancer epidemiology in the United States: racial, social, and economic factors. Cancer Epidemiol. 2009:65-83.
[6] Thakkar JP, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014;23.10:1985-1996.
[7] Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20.7:899-905.
[8] Chia SK, Ellard SL, Mates M, Welch S, Mihalcioiu C, Miller WH, et al. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Breast Cancer Res. 2017;19, no. 1:54.
[9] Chen HM, Tsai CH, Hung WC. Foretinib inhibits angiogenesis, lymphangiogenesis and tumor growth of pancreatic cancer in vivo by decreasing VEGFR-2/3 and TIE-2 signaling. Oncotarget. 2015;6, no. 17:14940.
[10] Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36, no. 13 :1621-1630.
[11] González-Arriaga P, Pascual T, García-Alvarez A, Fernández-Somoano A, López-Cima MF, Tardón A. Genetic polymorphisms in MMP 2, 9 and 3 genes modify lung cancer risk and survival. BMC cancer. 2012;12, no. 1:121.
[12] Kesanakurti D, et al. Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma. Cell Death Dis. 2012;3.12:e445.
[13] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 2001. p. 402-408.
[14] Hawkes SP, Hongxia Li, Taniguchi GT. Zymography and reverse zymography for detecting MMPs and TIMPs. In Matrix metalloproteinase protocols, Humana Press, Totowa, NJ, 2010. p. 257-269.
[15] Jung TY, et al. Immunological characterization of glioblastoma cells for immunotherapy. Anticancer Res. 2013;33.6:2525-2533.
[16] Zillhardt M, et al. Foretinib (GSK1363089), an orally available multikinase inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis. Clinical Cancer Res. 2011;17.12:4042-4051.
[17] Nelson SK, et al. Et-070. Foretinib Inhibits Invasion, A Hallmark Of Malignancy, In Glioblastoma Multiforme. Neuro Oncol. 2013;15.suppl_3:iii37-iii61.
[18] Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455.7216:1061.
[19] Lu KV, Jong KA, Rajasekaran AK, Cloughesy TF, Mischel PS. Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line. Laboratory investigation. 2004;84??:8.
[20] Badiga AV, et al. MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PloS One. 2011;6.6:e20614.
[21] Momeny M, et al. Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells. Sci Rep. 2017;7:44075.
[2] Ostrom QT, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15.suppl_2:ii1-ii56.
[3] Louis DN, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114.2:97-109.
[4] McKinley BP, et al. The impact of age and gender on the incidence of glial tumors in New York state from 1976–1995. J Neurosurg. 2000;93.6:932-939.
[5] Sloane D. Cancer epidemiology in the United States: racial, social, and economic factors. Cancer Epidemiol. 2009:65-83.
[6] Thakkar JP, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014;23.10:1985-1996.
[7] Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20.7:899-905.
[8] Chia SK, Ellard SL, Mates M, Welch S, Mihalcioiu C, Miller WH, et al. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Breast Cancer Res. 2017;19, no. 1:54.
[9] Chen HM, Tsai CH, Hung WC. Foretinib inhibits angiogenesis, lymphangiogenesis and tumor growth of pancreatic cancer in vivo by decreasing VEGFR-2/3 and TIE-2 signaling. Oncotarget. 2015;6, no. 17:14940.
[10] Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36, no. 13 :1621-1630.
[11] González-Arriaga P, Pascual T, García-Alvarez A, Fernández-Somoano A, López-Cima MF, Tardón A. Genetic polymorphisms in MMP 2, 9 and 3 genes modify lung cancer risk and survival. BMC cancer. 2012;12, no. 1:121.
[12] Kesanakurti D, et al. Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma. Cell Death Dis. 2012;3.12:e445.
[13] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 2001. p. 402-408.
[14] Hawkes SP, Hongxia Li, Taniguchi GT. Zymography and reverse zymography for detecting MMPs and TIMPs. In Matrix metalloproteinase protocols, Humana Press, Totowa, NJ, 2010. p. 257-269.
[15] Jung TY, et al. Immunological characterization of glioblastoma cells for immunotherapy. Anticancer Res. 2013;33.6:2525-2533.
[16] Zillhardt M, et al. Foretinib (GSK1363089), an orally available multikinase inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis. Clinical Cancer Res. 2011;17.12:4042-4051.
[17] Nelson SK, et al. Et-070. Foretinib Inhibits Invasion, A Hallmark Of Malignancy, In Glioblastoma Multiforme. Neuro Oncol. 2013;15.suppl_3:iii37-iii61.
[18] Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455.7216:1061.
[19] Lu KV, Jong KA, Rajasekaran AK, Cloughesy TF, Mischel PS. Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line. Laboratory investigation. 2004;84??:8.
[20] Badiga AV, et al. MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PloS One. 2011;6.6:e20614.
[21] Momeny M, et al. Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells. Sci Rep. 2017;7:44075.