IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
THROMBOSPONDIN-1 (TSP1) MIMETIC PEPTIDES TREATMENT REDUCES TUMOR GROWTH AND SERUM PROLACTIN LEVELS IN ESTRADIOL-INDUCED PROLACTINOMAS
Autor/es:
RECOUVREUX MV; BECU-VILLALOBOS D; DÍAZ TORGA G
Lugar:
Dourado
Reunión:
Simposio; First Brazilian International Symposium on Integrative Neuroendocrinology; 2011
Institución organizadora:
International Neuroendocrine Federation
Resumen:
Prolactin secreting adenomas are the most frequent among pituitary tumors. They are usually benign and can be treated with dopaminergic agents. Nevertheless, 15% of these tumors are resistant to classical pharmacological therapy, and require extirpation. Alternative therapies would be desired for these tumors. Thrombospondin 1 (TSP1) is a large matrix glycoprotein, with antiangiogenic and anti-tumoral functions in different tissues due, in part, to its ability to activate TGFb1, releasing the mature cytokine from its latent complexes. In the pituitary gland, TGFb1 has inhibitory effects on lactotrope growth rate and prolactin secretion. Both TSP1 and TGFb1 expression are decreased in prolactinomas induced by diethylstilbestrol (DES) pellet implantation in rats. Our hypothesis is that recovering TSP1 and TGFb1 activity would be effective in inhibiting tumor growth in this model.  In preliminary in vitro assays we found that incubation with the TSP1 mimetic peptide ABT510 (1uM, Abbot) increased TGFb1 expression and inhibited prolactin (PRL) secretion in control and DES-treated pituitary cells in culture. The aim of our study was to test the in vivo therapeutic potential of two TSP-1mimetic peptides, ABT510 and ABT898, on prolactinomas developed after 4 weeks of DES treatment in female rats.  Two weeks after DES implant, rats were injected twice a week during two weeks with vehicle, ABT 510 or ABT898 (100mg/kg ip). Both TSP1 analogues were effective in decreasing pituitary tumor size and PRL serum levels. PCNA expression was also reduced after treatment with ABT510 and ABT 898, indicating a decrease in the tumor proliferation rate. Finally, we found that both peptides were able to restore PSMAD2/3 expression, suggesting a recovering of TGFb1 activity. Although further studies are necessary, our data suggest that TSP1 analogues might be good candidates as alternative treatment in dopaminergic resistant prolactinomas.