Monia Orciani1, Miriam Caffarini2, Giulia Sorgentoni2, Riccardo Antonio Ricciuti3, Giorgio Arnaldi4, Roberto Di Primio2. 1. Department of Clinical and Molecular Sciences - Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy. m.orciani@univpm.it. 2. Department of Clinical and Molecular Sciences - Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy. 3. Department of Neurological, Medical and Surgery Sciences, Azienda Ospedali Riuniti di Ancona, Via Conca, 60126, Ancona, Italy. 4. Department of Clinical and Molecular Sciences - Endocrinology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy.
Abstract
PURPOSE: Progenitor mesenchymal cells (PMCs) have been found also in epithelial tumors and may derive from cancer stem cells (CSCs) by EMT mechanism. In this scenario, the effects of traditionally drugs on PMCs become of primary concern for therapeutic approaches. Previously, we isolated PMCs from acromegalic (GHomas) and not-functioning pituitary adenomas (NFPAs). Here we evaluate: (1) the role of EMT on their origin; (2) the presence of the somatostatin receptors (SSTR1-5); (3) the effects of somatostatin (SST) and its analogues (SSAs) on PMCs proliferation, apoptosis and SSTR1-5 expression. METHODS: PMCs were isolated from GHomas and NFPAs; the expression of E-CADHERIN and TGFβRII (referred to EMT), the expression of the SSTR1-5 as well as the proliferation and apoptosis were tested before and after drugs administration. RESULTS: Results show a decrease of E-CADHERIN and an increase of TGFβRII, confirming an EMT involvement; SSTR1-5 are more expressed by PMCs from GHomas than from NFPAs. SST and SSAs administration does not affect cell proliferation and SSTR1-5 expression on PMCs from NFPAs while in PMCs from GHomas, cell proliferation showed a marked decrease and a corresponding increase in the expression of SSTR1-2. Apoptosis rate and EMT were not affected by drugs administration. CONCLUSIONS: Results indicate as EMT may be related to the presence of PMCs on pituitary tumors; SSAs, currently used in the management of human GHomas, exert anti-proliferative effect also in PMCs that, because of their derivation from CSCs, may be a new meaningful target for drugs treatment.
PURPOSE: Progenitor mesenchymal cells (PMCs) have been found also in epithelial tumors and may derive from cancer stem cells (CSCs) by EMT mechanism. In this scenario, the effects of traditionally drugs on PMCs become of primary concern for therapeutic approaches. Previously, we isolated PMCs from acromegalic (GHomas) and not-functioning pituitary adenomas (NFPAs). Here we evaluate: (1) the role of EMT on their origin; (2) the presence of the somatostatin receptors (SSTR1-5); (3) the effects of somatostatin (SST) and its analogues (SSAs) on PMCs proliferation, apoptosis and SSTR1-5 expression. METHODS: PMCs were isolated from GHomas and NFPAs; the expression of E-CADHERIN and TGFβRII (referred to EMT), the expression of the SSTR1-5 as well as the proliferation and apoptosis were tested before and after drugs administration. RESULTS: Results show a decrease of E-CADHERIN and an increase of TGFβRII, confirming an EMT involvement; SSTR1-5 are more expressed by PMCs from GHomas than from NFPAs. SST and SSAs administration does not affect cell proliferation and SSTR1-5 expression on PMCs from NFPAs while in PMCs from GHomas, cell proliferation showed a marked decrease and a corresponding increase in the expression of SSTR1-2. Apoptosis rate and EMT were not affected by drugs administration. CONCLUSIONS: Results indicate as EMT may be related to the presence of PMCs on pituitary tumors; SSAs, currently used in the management of human GHomas, exert anti-proliferative effect also in PMCs that, because of their derivation from CSCs, may be a new meaningful target for drugs treatment.
Authors: A Gigante; S Manzotti; C Bevilacqua; M Orciani; R Di Primio; M Mattioli-Belmonte Journal: Eur J Histochem Date: 2008 Jul-Sep Impact factor: 3.188
Authors: Katja Kiseljak-Vassiliades; Mei Xu; Taylor S Mills; Elizabeth E Smith; Lori J Silveira; Kevin O Lillehei; Janice M Kerr; B K Kleinschmidt-DeMasters; Margaret E Wierman Journal: Mol Cell Endocrinol Date: 2015-09-21 Impact factor: 4.102
Authors: M Orciani; S Davis; G Appolloni; R Lazzarini; M Mattioli-Belmonte; R A Ricciuti; M Boscaro; R Di Primio; G Arnaldi Journal: Cancer Gene Ther Date: 2014-12-19 Impact factor: 5.987