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  • Title: Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.
    Author: Ibáñez-Costa A, Rivero-Cortés E, Vázquez-Borrego MC, Gahete MD, Jiménez-Reina L, Venegas-Moreno E, de la Riva A, Arráez MÁ, González-Molero I, Schmid HA, Maraver-Selfa S, Gavilán-Villarejo I, García-Arnés JA, Japón MA, Soto-Moreno A, Gálvez MA, Luque RM, Castaño JP.
    Journal: J Endocrinol; 2016 Nov; 231(2):135-145. PubMed ID: 27587848.
    Abstract:
    Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca2+ signaling ([Ca2+]i), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca2+]i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca2+]i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response.
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