Androgen-independent prostate carcinoma is characterized by a high proliferation rate and by a strong metastatic behavior. We have previously shown that GnRH agonists exert a direct and specific inhibitory action on the proliferation of androgen-independent prostate cancer cells (DU 145). These compounds mainly act by interfering with the mitogenic activity of growth factors, such as the insulin-like growth factor-I (IGF-I). The present experiments were performed to clarify whether GnRH agonists might also affect the migratory and the invasive behavior of androgen-independent prostate cancer cells and to define their mechanism of action. First we showed that the GnRH agonist Leuprolide reduces the migration of DU 145 cells towards a chemoattractant and their ability to invade a reconstituted basement membrane. Experiments were then performed to clarify whether the GnRH agonist might act by interfering with the pro-metastatic activity of IGF-I. We found that, in androgen-independent prostate cancer cells, Leuprolide: a) interferes with the IGF-I system (receptor protein expression and tyrosine-phosphorylation); b) abrogates the IGF-I-induced phosphorylation of Akt (a kinase previously shown by us to mediate the pro-metastatic activity of IGF-I in prostate cancer cells); c) counteracts the migration and the invasive activity of the cells stimulated by IGF-I; d) abolishes the effects of IGF-I on cell morphology, on actin cytoskeleton organization and on alpha v beta 3 integrin expression/cellular localization. These data indicate that GnRH agonists, in addition to their well known antiproliferative effect, can also exert a significant inhibitory activity on the migratory and invasive behavior of androgen- independent prostate cancer cells, expressing the GnRH receptor. GnRH agonists act by interfering with the pro-metastatic activity of the growth factor IGF-I.
Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I / M. Montagnani Marelli, R.M. Moretti, S. Mai, P. Procacci, P. Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 30:1(2007), pp. 261-271.
|Titolo:||Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I|
MONTAGNANI MARELLI, MARINA (Primo)
MORETTI, ROBERTA MANUELA (Secondo)
PROCACCI, PATRIZIA (Penultimo)
LIMONTA, PATRIZIA (Ultimo)
|Parole Chiave:||prostate cancer; gonadotropin-releasing hormone; insulin-like growth factor-I; migration; invasion|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
Settore BIO/17 - Istologia
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||2007|
|Appare nelle tipologie:||01 - Articolo su periodico|