1. Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.
- Author
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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, and Castaño JP more...
- Subjects
- ACTH-Secreting Pituitary Adenoma drug therapy, ACTH-Secreting Pituitary Adenoma metabolism, ACTH-Secreting Pituitary Adenoma pathology, Adenoma drug therapy, Adenoma metabolism, Adenoma pathology, Antineoplastic Agents, Hormonal adverse effects, Calcium Signaling drug effects, Cell Survival drug effects, Cells, Cultured, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic drug effects, Growth Hormone-Secreting Pituitary Adenoma drug therapy, Growth Hormone-Secreting Pituitary Adenoma metabolism, Growth Hormone-Secreting Pituitary Adenoma pathology, Humans, Male, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Octreotide adverse effects, Pituitary Gland metabolism, Pituitary Gland pathology, Pituitary Neoplasms metabolism, Pituitary Neoplasms pathology, Prolactinoma drug therapy, Prolactinoma metabolism, Prolactinoma pathology, Protein Isoforms agonists, Protein Isoforms genetics, Protein Isoforms metabolism, Receptors, Somatostatin genetics, Receptors, Somatostatin metabolism, Somatostatin adverse effects, Somatostatin pharmacology, Tumor Cells, Cultured, Antineoplastic Agents, Hormonal pharmacology, Neoplasm Proteins agonists, Octreotide pharmacology, Pituitary Gland drug effects, Pituitary Neoplasms drug therapy, Receptors, Somatostatin agonists, Somatostatin analogs & derivatives
- 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 Ca
2+ 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., (© 2016 Society for Endocrinology.) more...- Published
- 2016
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