Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice

  • Authors:
    • Jennifer L. Owen
    • Marta Torroella-Kouri
    • Vijaya Iragavarapu-Charyulu
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijmm.21.1.125
  • Pages: 125-134
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Abstract

Matrix metalloproteinases (MMPs) are a family of extracellular proteinases whose contributions to cancer progression have been studied because of their matrix-degrading abilities and elevated expression in advanced stage tumors. Recent findings suggest a role for MMPs during the multiple stages of tumor progression including establishment and growth, migration, invasion, metastasis, and angiogenesis. MMP-9 regulation at the molecular level can be studied by measuring the effect(s) of a variety of physiological and pharmacological agents on cells. Multiple signaling molecules such as protein kinase C, pertussis toxin-sensitive guanine nucleotide-binding protein G, and protein tyrosine kinases are known to mediate the secretion of MMPs in cell lines. We previously reported an upregulation of MMP-9 in T cells of mammary tumor-bearing mice. In this study, pharmacologic inhibitors were used to dissect the signaling pathways involved in the upregulation of MMP-9 in the splenic T cells of normal and mammary tumor-bearing mice. Staurosporine, a protein kinase inhibitor, stimulated MMP-9 secretion by normal T lymphocytes, while the constitutively high levels of MMP-9 produced by tumor bearers' T cells were decreased by Genistein, a specific tyrosine kinase inhibitor, and Rottlerin, a PKC inhibitor. Using a NF-κB specific probe to the murine MMP-9 promoter, electromobility shift assays of nuclear proteins from normal and tumor bearers' splenic T cells revealed a pattern of higher intensity bands from the tumor bearers' nuclear extracts, indicating a greater amount of these transcription factors bound to the recognition motif. When mammary tumor bearers' T cells were cultured with the NF-κB inhibitors, N-p-Tosyl-L-lysine chloromethyl ketone hydrochloride and Bay 11-7082, there was a subsequent decreased production of MMP-9. These results suggest that the tumor burden may be activating various signaling pathways within splenic T lymphocytes to upregulate MMP-9 expression.

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January 2008
Volume 21 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Owen JL, Torroella-Kouri M and Iragavarapu-Charyulu V: Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice. Int J Mol Med 21: 125-134, 2008
APA
Owen, J.L., Torroella-Kouri, M., & Iragavarapu-Charyulu, V. (2008). Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice. International Journal of Molecular Medicine, 21, 125-134. https://doi.org/10.3892/ijmm.21.1.125
MLA
Owen, J. L., Torroella-Kouri, M., Iragavarapu-Charyulu, V."Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice". International Journal of Molecular Medicine 21.1 (2008): 125-134.
Chicago
Owen, J. L., Torroella-Kouri, M., Iragavarapu-Charyulu, V."Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice". International Journal of Molecular Medicine 21, no. 1 (2008): 125-134. https://doi.org/10.3892/ijmm.21.1.125