Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Maria Chiara Zatelli, Daniela Piccin, Cristina Vignali, Federico Tagliati, Maria Rosaria Ambrosio, Marta Bondanelli, Vincenzo Cimino, Antonio Bianchi, Herbert A. Schmid, Massimo Scanarini, Alfredo Pontecorvi, Laura De Marinis, Giulio Maira, Ettore C. Degli Uberti

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Abstract

Somatostatin (SRIF) analogs have been employed in medical therapy of non-functioning pituitary adenomas (NFA), with contrasting results. Previous evidence showed that SRIF can exert its antiproliferative effects by reducing vascular endothelial growth factor (VEGF) secretion and action, and that VEGF expression may be related to pituitary tumor growth. The aim of our study was to clarify the possible effects of a multireceptor SRIF ligand on VEGF secretion and cell proliferation in human NFA primary cultures. We assessed the expression of SRIF receptors (SSTR1-5), the in vitro effects on VEGF secretion, and on cell viability of SRIF and of the stable SRIF analog pasireotide (SOM230), which activates SSTR1, 2, 3, and 5. Twenty-five NFA were examined by RT-PCR for expression of α-subunit, SSTR, VEGF, and VEGF receptors 1 (VEGF-R1) and 2 (VEGF-R2). Primary cultures were tested with SRIF and with pasireotide. All NFA samples expressed α-sub, VEGF and VEGFR-1 and 2, while SSTR expression pattern was highly variable. Two different groups were identified according to VEGF secretion inhibition by SRIF. VEGF secretion and cell viability were reduced by SRIF and pasireotide in the 'responder' group, but not in the 'non-responder' group, including NFA expressing SSTR5. SRIF and pasireotide completely blocked forskolin-induced VEGF secretion. In addition, SRIF and pasireotide completely abrogated the promoting effects of VEGF on NFA cell viability. Our data demonstrate that pasireotide can inhibit NFA cell viability by inhibiting VEGF secretion, and suggest that the multireceptor-SSTR agonist pasireotide might be useful in medical therapy of selected NFA.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalEndocrine-Related Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - Mar 2007

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ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Zatelli, M. C., Piccin, D., Vignali, C., Tagliati, F., Ambrosio, M. R., Bondanelli, M., Cimino, V., Bianchi, A., Schmid, H. A., Scanarini, M., Pontecorvi, A., De Marinis, L., Maira, G., & Degli Uberti, E. C. (2007). Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocrine-Related Cancer, 14(1), 91-102. https://doi.org/10.1677/ERC-06-0026