Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness throught the inhibition of a3 integrin and MMP-2 expression and activity
Articolo
Data di Pubblicazione:
2008
Citazione:
Gonadotropin-releasing hormone agonists suppress melanoma cell motility and invasiveness throught the inhibition of a3 integrin and MMP-2 expression and activity / R.M. Moretti, M. Montagnani Marelli, S. Mai, P. Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 33:2(2008), pp. 405-413. [10.3892/ijo_00000022]
Abstract:
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).
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Gonadotropin-releasing hormone; Integrins; Invasion; Matrix metalloproteinase-2; Melanoma; Migration
Elenco autori:
R.M. Moretti, M. Montagnani Marelli, S. Mai, P. Limonta
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