Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness through the inhibition of α3 integrin and MMP-2 expression and activity

  • Authors:
    • Roberta M. Moretti
    • Marina Montagnani Marelli
    • Stefania Mai
    • Patrizia Limonta
  • View Affiliations

  • Published online on: August 1, 2008     https://doi.org/10.3892/ijo_00000022
  • Pages: 405-413
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Abstract

Cutaneous melanoma represents the leading cause of skin cancer deaths. The prognosis of highly aggressive, metastatic melanoma is still very poor, due to the resistance of the disseminated tumor to existing therapies. The clarification of the molecular mechanisms regulating melanoma growth and progression might help identify novel molecular targets for the development of new therapeutic interventions. We previously showed that gonadotropin-releasing hormone (GnRH) receptors are expressed in melanoma cells; activation of these receptors by means of GnRH agonists significantly reduces cell proliferation. In the current study, we first showed that GnRH agonists significantly reduced the metastatic behavior of melanoma cells in terms of both cell motility (haptotactic assay using laminin as the chemoattractant) and invasiveness (cell invasion assay evaluating the capacity of the cells to invade a reconstituted extracellular matrix barrier). On the basis of this observation, we then investigated the molecular mechanisms underlying the antimetastatic activity of GnRH agonists. We found that, in melanoma cells, a) the activity of the α3 integrin subunit is crucial for the migratory behavior of the cells; b) GnRH agonists significantly reduced α3 integrin expression (Western blotting and immunofluorescence studies); c) GnRH agonists significantly reduced MMP-2 expression (comparative RT-PCR) and activity (zymographic analysis performed on cell culture media). These data indicate that GnRH agonists, in addition to the previously reported antiproliferative effect, elicit a strong inhibitory activity on the migratory/invasive behavior of melanoma cells expressing GnRH receptors. These compounds reduce the metastatic potential of melanoma cells by interfering with the expression/activity of cell adhesion molecules (α3 integrin) and matrix metalloproteinase (MMP-2).

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August 2008
Volume 33 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Moretti RM, Montagnani Marelli M, Mai S and Limonta P: Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness through the inhibition of α3 integrin and MMP-2 expression and activity. Int J Oncol 33: 405-413, 2008
APA
Moretti, R.M., Montagnani Marelli, M., Mai, S., & Limonta, P. (2008). Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness through the inhibition of α3 integrin and MMP-2 expression and activity. International Journal of Oncology, 33, 405-413. https://doi.org/10.3892/ijo_00000022
MLA
Moretti, R. M., Montagnani Marelli, M., Mai, S., Limonta, P."Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness through the inhibition of α3 integrin and MMP-2 expression and activity". International Journal of Oncology 33.2 (2008): 405-413.
Chicago
Moretti, R. M., Montagnani Marelli, M., Mai, S., Limonta, P."Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness through the inhibition of α3 integrin and MMP-2 expression and activity". International Journal of Oncology 33, no. 2 (2008): 405-413. https://doi.org/10.3892/ijo_00000022