title: Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.
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+]imore 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+]iin 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.
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Alejandro
authors: A
authors: Ibáñez-Costa
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Esther
authors: E
authors: Rivero-Cortés
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Mari C
authors: MC
authors: Vázquez-Borrego
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Manuel D
authors: MD
authors: Gahete
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Department of Morphological SciencesUniversidad de Córdoba, Córdoba, Spain.
authors: Luis
authors: L
authors: Jiménez-Reina
authors: Metabolism and Nutrition UnitHospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors: Eva
authors: E
authors: Venegas-Moreno
authors: Service of NeurosurgeryHospital Universitario Reina Sofía, Córdoba, Spain.
authors: Andrés
authors: A
authors: de la Riva
authors: Neurosurgical DepartmentCarlos Haya Hospital, Málaga, Spain.
authors: Miguel Ángel
authors: MÁ
authors: Arráez
authors: Department of Endocrinology and NutritionCarlos Haya Hospital, Málaga, Spain.
authors: Inmaculada
authors: I
authors: González-Molero
authors: Novartis Pharma AGNovartis Institutes for Biomedical Research, Oncology, CH-4057 Basel, Switzerland.
authors: Herbert A
authors: HA
authors: Schmid
authors: Service of Endocrinology and NutritionHospital Clínico Universitario Virgen de la Victoria, Málaga, Spain.
authors: Silvia
authors: S
authors: Maraver-Selfa
authors: Endocrinology and Nutrition UnitHospital Universitario Puerta del Mar, Cádiz, Spain.
authors: Inmaculada
authors: I
authors: Gavilán-Villarejo
authors: Department of Endocrinology and NutritionCarlos Haya Hospital, Málaga, Spain.
authors: Juan Antonio
authors: JA
authors: García-Arnés
authors: Department of PathologyHospital Universitario Virgen del Rocío, Seville, Spain.
authors: Miguel A
authors: MA
authors: Japón
authors: Metabolism and Nutrition UnitHospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors: Alfonso
authors: A
authors: Soto-Moreno
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain.|Service of Endocrinology and NutritionHospital Universitario Reina Sofía, Córdoba, Spain.
authors: María A
authors: MA
authors: Gálvez
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain raul.luque@uco.es justo@uco.es.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Raúl M
authors: RM
authors: Luque
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Córdoba, Spain raul.luque@uco.es justo@uco.es.|Department of Cell BiologyPhysiology and Immunology, Universidad de Córdoba, Córdoba, Spain.|Hospital Universitario Reina SofíaCórdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn)Córdoba, Spain.
authors: Justo P
authors: JP
authors: Castaño
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015282:Octreotide / Q000009:adverse effects / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015175:Prolactinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide
keywords: cell signaling; gene expression; pituitary; pituitary adenoma; somatostatin