In its phase of androgen-independence, prostate carcinoma is characterized by a high proliferation rate and by a strong ability to give rise to metastases. IGF-I has been shown to exert a potent mitogenic action on prostate cancer. We investigated whether IGF-I might also affect the motility of prostate cancer cells and defined the mechanism of action. We found that IGF-I promotes the migratory capacity of androgen-independent prostate cancer cells through the activation of its specific receptor, IGF-IR. This effect was accompanied by a change in cell morphology (as revealed by scanning electron microscopy), and by a rearrangement of the actin cytoskeleton. The treatment of cells with the PI3-K inhibitor, LY294002, counteracted the pro-migratory activity of IGF-I. Experiments were then performed to clarify whether the integrin, alpha v beta 3, could be involved in the action of IGF-I. We demonstrated that: a) the IGF-I-induced migration of cells is completely antagonized by an antibody specifically blocking the function of alpha v beta 3; b) IGF-I increases alpha v beta 3 immunofluorescence at the level of cell membranes, and this effect is counteracted by LY294002; and c) IGF-I increases alpha v beta 3 protein levels. Our results demonstrate that IGF-I promotes the motility of androgen-independent prostate cancer cells by modulating alpha v beta 3 integrin activation/expression; these effects are mediated by the PI3-K/Akt signaling pathway. This study: a) supports a crucial role for IGF-I in the progression of the pathology towards the highly metastatic phase; and b) provides an additional rationale basis for the development of therapeutic strategies directed at the IGF-I/IGF-IR system in the treatment of androgen-independent prostate cancer.
Insulin-like growth factor-I promotes migration in human androgen-independent prostate cancer cells via the alpha v beta 3 integrin and PI3-K/Akt signaling / M. Montagnani Marelli, R.M. Moretti, P. Procacci, M. Motta, P. Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 28:3(2006), pp. 723-730.
|Titolo:||Insulin-like growth factor-I promotes migration in human androgen-independent prostate cancer cells via the alpha v beta 3 integrin and PI3-K/Akt signaling|
MONTAGNANI MARELLI, MARINA (Primo)
MORETTI, ROBERTA MANUELA (Secondo)
MOTTA, MARCELLA (Penultimo)
LIMONTA, PATRIZIA (Ultimo)
|Parole Chiave:||IGF-I; prostate cancer; cell motility; integrins; PI3-K/Akt|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
Settore BIO/17 - Istologia
Settore BIO/09 - Fisiologia
|Data di pubblicazione:||2006|
|Appare nelle tipologie:||01 - Articolo su periodico|