title: The expression of the truncated isoform of somatostatin receptor subtype 5 associates with aggressiveness in medullary thyroid carcinoma cells.
abstract: The truncated somatostatin receptor variant sst5TMD4 associates with increased invasiveness and aggressiveness in breast cancer. We previously found that sst5 activation may counteract sst2 selective agonist effects in a medullary thyroid carcinoma (MTC) cell line, the TT cells, and that sst5TMD4 is overexpressed in poorly differentiated thyroid cancers. The purpose of this study is to evaluate sst5TMD4 expression in a series of human MTC and to explore the functional role of sst5TMD4 in TT cells. We evaluated sst5TMD4 and sst5 expression in 36 MTC samples. Moreover, we investigated the role of sst5TMD4 in TT cells evaluating cell number, DNA synthesis, free cytosolic calcium concentration ([Ca(2+)]i), calcitonin and vascular endothelial growth factor levels, cell morphology, protein expression, and invasion. We found that in MTC the balance between sst5TMD4 and sst5 expression influences disease stage. sst5TMD4 overexpression in TT cells confers a greater growth capacity, blocks sst2 agonist-induced antiproliferative effects, modifies the cell phenotype, decreases E-cadherin and phosphorylated β-catenin levels, increases vimentin, total β-catenin and phosphorylated GSK3B levels (in keeping with the development of epithelial to mesenchymal transition), and confers a greater invasion capacity. This is the first evidence indicating that sst5TMD4 is expressed in human MTC cells, where it associates with more aggressive behavior, suggesting that sst5TMD4 might play a functionally relevant role.
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors: Daniela
authors: D
authors: Molè
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.|Laboratorio in rete del Tecnopolo "Tecnologie delle terapie avanzate" (LTTA), University of Ferrara, Ferrara, Italy.
authors: Erica
authors: E
authors: Gentilin
authors: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, University of Cordoba, 14014, Córdoba, Spain.
authors: Alejandro
authors: A
authors: Ibañez-Costa
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors: Teresa
authors: T
authors: Gagliano
authors: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, University of Cordoba, 14014, Córdoba, Spain.
authors: Manuel D
authors: MD
authors: Gahete
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors: Federico
authors: F
authors: Tagliati
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors: Roberta
authors: R
authors: Rossi
authors: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Giustiniani 2, Padua, Italy.
authors: Maria Rosa
authors: MR
authors: Pelizzo
authors: Depatment of Surgery, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors: Giancarlo
authors: G
authors: Pansini
authors: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, University of Cordoba, 14014, Córdoba, Spain.
authors: Raúl M
authors: RM
authors: Luque
authors: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, University of Cordoba, 14014, Córdoba, Spain.
authors: Justo P
authors: JP
authors: Castaño
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.|Laboratorio in rete del Tecnopolo "Tecnologie delle terapie avanzate" (LTTA), University of Ferrara, Ferrara, Italy.
authors: Ettore
authors: E
authors: degli Uberti
authors: Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy. ztlmch@unife.it.|Laboratorio in rete del Tecnopolo "Tecnologie delle terapie avanzate" (LTTA), University of Ferrara, Ferrara, Italy. ztlmch@unife.it.
authors: Maria Chiara
authors: MC
authors: Zatelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5
keywords: Medullary thyroid carcinoma; TT cells; sst5; sst5TMD4