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The influence of opioid peptides on matrix metalloproteinase-9 and urokinase plasminogen activator expression in three cancer cell lines

  • Molecular Biology of the Cell
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Abstract

Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) regulate proteolysis of the extracellular matrix (ECM) and as a consequence are involved in a number of physiological and pathological states, including cancer. A crucial feature of cancer progression and metastasis is the disruption of the ECM and spreading of proliferating cancer cells. Over-expression of MMPs and uPA is common for most types of cancers and correlates well with the adverse prognosis. Compounds able to modulate the activity of these proteolytic enzymes may become important agents in cancer therapy. In the present study, we examined the effect of the μ-opioid receptor selective peptide, morphiceptin, and its two synthetic analogs on mRNA and protein levels of MMP-9 and uPA in three human cancer cell lines: MCF-7, HT-29, and SHSY5Y. Our findings indicate that in all three cell lines morphiceptin and its analogs attenuated MMP-9 expression and secretion and that this effect is not mediated by opioid receptors but is under control of the nitric oxide system. On the other hand, tested opioids up-regulated uPA levels through a mechanism that involved opioid-receptors. Different pathways by which opioid peptides exert their action in cancer cells can explain their contradictory influence on the level of cancer markers.

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Abbreviations

ECM:

extracellular matrix

eNOS:

endothelial nitric oxide synthase

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

MMPs:

matrix metalloproteinases

MMP-2:

gelatinase A

MMP-9:

gelatinase B

NO:

nitric oxide

PBS:

phosphate buffered saline

uPA:

urokinase plasminogen activator

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Authors and Affiliations

  1. Department of Biomolecular Chemistry, Medical University of Lodz, Lodz, 92-215, Poland

    K. Gach, A. Wyrębska & A. Janecka

  2. Department of Biochemistry, Medical University of Lodz, Lodz, 92-215, Poland

    J. Szemraj

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  1. K. Gach
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  2. A. Wyrębska
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  3. J. Szemraj
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  4. A. Janecka
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Correspondence to A. Janecka.

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Gach, K., Wyrębska, A., Szemraj, J. et al. The influence of opioid peptides on matrix metalloproteinase-9 and urokinase plasminogen activator expression in three cancer cell lines. Mol Biol 46, 796–801 (2012). https://doi.org/10.1134/S0026893312060052

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  • DOI: https://doi.org/10.1134/S0026893312060052

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