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Title: Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.
Authors: Ibáñez-Costa, Alejandro
Rivero-Cortés, Esther
Vázquez-Borrego, Mari C
Gahete, Manuel D
Jiménez-Reina, Luis
Venegas-Moreno, Eva
de la Riva, Andrés
Arráez, Miguel Ángel
González-Molero, Inmaculada
Schmid, Herbert A
Maraver-Selfa, Silvia
Gavilán-Villarejo, Inmaculada
García-Arnés, Juan Antonio
Japón, Miguel A
Soto-Moreno, Alfonso
Gálvez, María A
Luque, Raúl M
Castaño, Justo P
Keywords: cell signaling;gene expression;pituitary;pituitary adenoma;somatostatin
metadata.dc.subject.mesh: ACTH-Secreting Pituitary Adenoma
Antineoplastic Agents, Hormonal
Calcium Signaling
Cell Survival
Cells, Cultured
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Growth Hormone-Secreting Pituitary Adenoma
Neoplasm Proteins
Pituitary Gland
Pituitary Neoplasms
Protein Isoforms
Receptors, Somatostatin
Tumor Cells, Cultured
Issue Date: 1-Sep-2016
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.
metadata.dc.identifier.doi: 10.1530/JOE-16-0332
Appears in Collections:Producción 2020

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