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Published in:

01-04-2017

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

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

Published in: Pituitary | Issue 2/2017

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.

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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

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

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)

Pawlikowski M, Mełeń-Mucha G (2004) Somatostatin analogs—from new molecules to new applications. Curr Opin Pharmacol 4:608–613CrossRefPubMed

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

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

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

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

Liu X, Fan D (2015) The epithelial–mesenchymal transition and cancer stem cells: functional and mechanistic links. Curr Pharm Des 21:1279–1291CrossRefPubMed

10.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Zhu X, Gleiberman AS, Rosenfeld MG (2007) Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87:933–963CrossRefPubMed

22.

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.

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.

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.

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.

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.

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.

van Roy F, Berx G (2008) The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65:3756–3788CrossRefPubMed

29.

Katsuno Y, Lamouille S, Derynck R (2013) TGF-β signaling and epithelial–mesenchymal transition in cancer progression. Curr Opin Oncol 25:76–84CrossRefPubMed

30.

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.

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.

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.

Florio T (2008) Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 13:822–840CrossRefPubMed

34.

War SA, Kumar U (2012) Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis. J Mol Signal 7:5CrossRefPubMedPubMedCentral

Title: Effects of somatostatin and its analogues on progenitor mesenchymal cells isolated from human pituitary adenomas
Authors: Monia Orciani
Miriam Caffarini
Giulia Sorgentoni
Riccardo Antonio Ricciuti
Giorgio Arnaldi
Roberto Di Primio
Publication date: 01-04-2017
Publisher: Springer US
Published in: Pituitary / Issue 2/2017
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI: https://doi.org/10.1007/s11102-016-0770-x

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