Skip to main content
Erschienen in: Pituitary 2/2017

28.10.2016

Effects of somatostatin and its analogues on progenitor mesenchymal cells isolated from human pituitary adenomas

verfasst von: Monia Orciani, Miriam Caffarini, Giulia Sorgentoni, Riccardo Antonio Ricciuti, Giorgio Arnaldi, Roberto Di Primio

Erschienen in: Pituitary | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S, Acromegaly Consensus Group (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10:243–248CrossRefPubMed Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S, Acromegaly Consensus Group (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10:243–248CrossRefPubMed
2.
Zurück zum Zitat Mazziotti G, Giustina A (2010) Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13:60–67CrossRefPubMed Mazziotti G, Giustina A (2010) Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13:60–67CrossRefPubMed
3.
Zurück zum Zitat Colao A, Auriemma RS, Pivonello R, Kasuki L, Gadelha MR (2015) Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary (Epub ahead of print) Colao A, Auriemma RS, Pivonello R, Kasuki L, Gadelha MR (2015) Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary (Epub ahead of print)
4.
Zurück zum Zitat Pawlikowski M, Mełeń-Mucha G (2004) Somatostatin analogs—from new molecules to new applications. Curr Opin Pharmacol 4:608–613CrossRefPubMed Pawlikowski M, Mełeń-Mucha G (2004) Somatostatin analogs—from new molecules to new applications. Curr Opin Pharmacol 4:608–613CrossRefPubMed
5.
Zurück zum Zitat Goodyer CG, Grigorakis SI, Patel YC, Kumar U (2004) Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus. Neuroscience 125:441–448CrossRefPubMed Goodyer CG, Grigorakis SI, Patel YC, Kumar U (2004) Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus. Neuroscience 125:441–448CrossRefPubMed
6.
Zurück zum Zitat Kiseljak-Vassiliades K, Xu M, Mills TS, Smith EE, Silveira LJ, Lillehei KO, Kerr JM, Kleinschmidt-DeMasters BK, Wierman ME (2015) Differential somatostatin receptor (SSTR) 1–5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors. Mol Cell Endocrinol 417:73–83CrossRefPubMedPubMedCentral Kiseljak-Vassiliades K, Xu M, Mills TS, Smith EE, Silveira LJ, Lillehei KO, Kerr JM, Kleinschmidt-DeMasters BK, Wierman ME (2015) Differential somatostatin receptor (SSTR) 1–5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors. Mol Cell Endocrinol 417:73–83CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Orciani M, Davis S, Appolloni G, Lazzarini R, Mattioli-Belmonte M, Ricciuti RA, Boscaro M, Di Primio R, Arnaldi G (2015) Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 22:9–16CrossRefPubMed Orciani M, Davis S, Appolloni G, Lazzarini R, Mattioli-Belmonte M, Ricciuti RA, Boscaro M, Di Primio R, Arnaldi G (2015) Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 22:9–16CrossRefPubMed
8.
Zurück zum Zitat Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA et al (2008) The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715CrossRefPubMedPubMedCentral Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA et al (2008) The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Liu X, Fan D (2015) The epithelial–mesenchymal transition and cancer stem cells: functional and mechanistic links. Curr Pharm Des 21:1279–1291CrossRefPubMed Liu X, Fan D (2015) The epithelial–mesenchymal transition and cancer stem cells: functional and mechanistic links. Curr Pharm Des 21:1279–1291CrossRefPubMed
10.
Zurück zum Zitat Sato R, Semba T, Saya H, Arima Y (2016) Stem cells and epithelial–mesenchymal transition (EMT) in cancer: biological implications and therapeutic targets. Stem Cells (Epub ahead of print) Sato R, Semba T, Saya H, Arima Y (2016) Stem cells and epithelial–mesenchymal transition (EMT) in cancer: biological implications and therapeutic targets. Stem Cells (Epub ahead of print)
11.
Zurück zum Zitat Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A et al (2008) Generation of breast cancer stem cells through epithelial–mesenchymal transition. PLoS One 3:e2888CrossRefPubMedPubMedCentral Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A et al (2008) Generation of breast cancer stem cells through epithelial–mesenchymal transition. PLoS One 3:e2888CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Orciani M, Lazzarini R, Scartozzi M, Bolletta E, Mattioli-Belmonte M, Scalise A, Di Benedetto G, Di Primio R (2013) The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants. Plast Reconstr Surg 132:899e–910eCrossRefPubMed Orciani M, Lazzarini R, Scartozzi M, Bolletta E, Mattioli-Belmonte M, Scalise A, Di Benedetto G, Di Primio R (2013) The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants. Plast Reconstr Surg 132:899e–910eCrossRefPubMed
13.
Zurück zum Zitat Orciani M, Mariggiò MA, Morabito C, Di Benedetto G, Di Primio R (2010) Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol 23:124–132CrossRefPubMed Orciani M, Mariggiò MA, Morabito C, Di Benedetto G, Di Primio R (2010) Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol 23:124–132CrossRefPubMed
14.
Zurück zum Zitat Salvolini E, Orciani M, Vignini A, Mattioli-Belmonte M, Mazzanti L, Di Primio R (2010) Skin-derived mesenchymal stem cells (S-MSCs) induce endothelial cell activation by paracrine mechanisms. Exp Dermatol 19:848–850CrossRefPubMed Salvolini E, Orciani M, Vignini A, Mattioli-Belmonte M, Mazzanti L, Di Primio R (2010) Skin-derived mesenchymal stem cells (S-MSCs) induce endothelial cell activation by paracrine mechanisms. Exp Dermatol 19:848–850CrossRefPubMed
15.
Zurück zum Zitat Campanati A, Orciani M, Consales V, Lazzarini R, Ganzetti G, Di Benedetto G, Di Primio R, Offidani A (2014) Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1–Th17/Th2 imbalance of psoriasis. Arch Dermatol Res 306:915–920CrossRefPubMed Campanati A, Orciani M, Consales V, Lazzarini R, Ganzetti G, Di Benedetto G, Di Primio R, Offidani A (2014) Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1–Th17/Th2 imbalance of psoriasis. Arch Dermatol Res 306:915–920CrossRefPubMed
16.
Zurück zum Zitat Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317CrossRefPubMed Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317CrossRefPubMed
17.
Zurück zum Zitat Halfon S, Abramov N, Grinblat B, Ginis I (2011) Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev 20:53–66CrossRefPubMed Halfon S, Abramov N, Grinblat B, Ginis I (2011) Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev 20:53–66CrossRefPubMed
18.
Zurück zum Zitat Trivanović D, Jauković A, Popović B, Krstić J, Mojsilović S, Okić-Djordjević I, Kukolj T, Obradović H, Santibanez JF, Bugarski D (2015) Mesenchymal stem cells of different origin: comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression. Life Sci 141:61–73CrossRefPubMed Trivanović D, Jauković A, Popović B, Krstić J, Mojsilović S, Okić-Djordjević I, Kukolj T, Obradović H, Santibanez JF, Bugarski D (2015) Mesenchymal stem cells of different origin: comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression. Life Sci 141:61–73CrossRefPubMed
19.
Zurück zum Zitat Mariotti C, Lazzarini R, Nicolai M, Saitta A, Orsini E, Orciani M, Di Primio R (2015) Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells. Cell Tissue Res 362:21–31CrossRefPubMed Mariotti C, Lazzarini R, Nicolai M, Saitta A, Orsini E, Orciani M, Di Primio R (2015) Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells. Cell Tissue Res 362:21–31CrossRefPubMed
20.
Zurück zum Zitat De Moraes DC, Vaisman M, Conceição FL, Ortiga-Carvalho TM (2012) Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors. J Endocrinol 215:239–245CrossRefPubMed De Moraes DC, Vaisman M, Conceição FL, Ortiga-Carvalho TM (2012) Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors. J Endocrinol 215:239–245CrossRefPubMed
21.
Zurück zum Zitat Zhu X, Gleiberman AS, Rosenfeld MG (2007) Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87:933–963CrossRefPubMed Zhu X, Gleiberman AS, Rosenfeld MG (2007) Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87:933–963CrossRefPubMed
22.
Zurück zum Zitat Lazzarini R, Olivieri F, Ferretti C, Mattioli-Belmonte M, Di Primio R, Orciani M (2014) mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin. Cell Tissue Res 355:121–130CrossRefPubMed Lazzarini R, Olivieri F, Ferretti C, Mattioli-Belmonte M, Di Primio R, Orciani M (2014) mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin. Cell Tissue Res 355:121–130CrossRefPubMed
23.
Zurück zum Zitat Pasquali D, Rossi V, Conzo G, Pannone G, Bufo P, De Bellis A, Renzullo A, Bellastella G, Colao A, Vallone G, Bellastella A, Sinisi AA (2008) Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells. J Mol Endocrinol 40:263–271PubMed Pasquali D, Rossi V, Conzo G, Pannone G, Bufo P, De Bellis A, Renzullo A, Bellastella G, Colao A, Vallone G, Bellastella A, Sinisi AA (2008) Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells. J Mol Endocrinol 40:263–271PubMed
24.
Zurück zum Zitat Salvolini E, Lucarini G, Zizzi A, Orciani M, Di Benedetto G, Di Primio R (2010) Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide. Arch Dermatol Res 302:367–374CrossRefPubMed Salvolini E, Lucarini G, Zizzi A, Orciani M, Di Benedetto G, Di Primio R (2010) Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide. Arch Dermatol Res 302:367–374CrossRefPubMed
25.
Zurück zum Zitat Orciani M, Trubiani O, Vignini A, Mattioli-Belmonte M, Di Primio R, Salvolini E (2009) Nitric oxide production during the osteogenic differentiation of human periodontal ligament mesenchymal stem cells. Acta Histochem 111:15–24CrossRefPubMed Orciani M, Trubiani O, Vignini A, Mattioli-Belmonte M, Di Primio R, Salvolini E (2009) Nitric oxide production during the osteogenic differentiation of human periodontal ligament mesenchymal stem cells. Acta Histochem 111:15–24CrossRefPubMed
26.
Zurück zum Zitat Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, Di Primio R (2008) Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells. Int J Immunopathol Pharmacol. 21:595–602CrossRefPubMed Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, Di Primio R (2008) Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells. Int J Immunopathol Pharmacol. 21:595–602CrossRefPubMed
27.
Zurück zum Zitat Gigante A, Manzotti S, Bevilacqua C, Orciani M, Di Primio R, Mattioli-Belmonte M (2008) Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials. Eur J Histochem 52:169–174CrossRefPubMed Gigante A, Manzotti S, Bevilacqua C, Orciani M, Di Primio R, Mattioli-Belmonte M (2008) Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials. Eur J Histochem 52:169–174CrossRefPubMed
28.
Zurück zum Zitat van Roy F, Berx G (2008) The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65:3756–3788CrossRefPubMed van Roy F, Berx G (2008) The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65:3756–3788CrossRefPubMed
29.
Zurück zum Zitat Katsuno Y, Lamouille S, Derynck R (2013) TGF-β signaling and epithelial–mesenchymal transition in cancer progression. Curr Opin Oncol 25:76–84CrossRefPubMed Katsuno Y, Lamouille S, Derynck R (2013) TGF-β signaling and epithelial–mesenchymal transition in cancer progression. Curr Opin Oncol 25:76–84CrossRefPubMed
30.
Zurück zum Zitat Batista DL, Zhang X, Gejman R, Ansell PJ, Zhoum Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA, Klibanski A (2006) The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 91:4482–4488CrossRefPubMed Batista DL, Zhang X, Gejman R, Ansell PJ, Zhoum Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA, Klibanski A (2006) The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 91:4482–4488CrossRefPubMed
31.
Zurück zum Zitat Zatelli MC, Piccin D, Bottoni A, Ambrosio MR, Margutti A, Padovani R, Scanarini M, Taylor JE, Culler MD, Cavazzini L, degli Uberti EC (2004) Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin a secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro. J Clin Endocrinol Metab 89:5181–5188CrossRefPubMed Zatelli MC, Piccin D, Bottoni A, Ambrosio MR, Margutti A, Padovani R, Scanarini M, Taylor JE, Culler MD, Cavazzini L, degli Uberti EC (2004) Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin a secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro. J Clin Endocrinol Metab 89:5181–5188CrossRefPubMed
32.
Zurück zum Zitat War SA, Somvanshi RK, Kumar U (2011) Somatostatin receptor-3 mediated intracellular signaling and apoptosis is regulated by its cytoplasmic terminal. Biochim Biophys Acta 1813:390–402CrossRefPubMed War SA, Somvanshi RK, Kumar U (2011) Somatostatin receptor-3 mediated intracellular signaling and apoptosis is regulated by its cytoplasmic terminal. Biochim Biophys Acta 1813:390–402CrossRefPubMed
33.
Zurück zum Zitat Florio T (2008) Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 13:822–840CrossRefPubMed Florio T (2008) Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 13:822–840CrossRefPubMed
34.
Zurück zum Zitat War SA, Kumar U (2012) Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis. J Mol Signal 7:5CrossRefPubMedPubMedCentral War SA, Kumar U (2012) Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis. J Mol Signal 7:5CrossRefPubMedPubMedCentral
Metadaten
Titel
Effects of somatostatin and its analogues on progenitor mesenchymal cells isolated from human pituitary adenomas
verfasst von
Monia Orciani
Miriam Caffarini
Giulia Sorgentoni
Riccardo Antonio Ricciuti
Giorgio Arnaldi
Roberto Di Primio
Publikationsdatum
28.10.2016
Verlag
Springer US
Erschienen in
Pituitary / Ausgabe 2/2017
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-016-0770-x

Weitere Artikel der Ausgabe 2/2017

Pituitary 2/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.