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.