Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors

E. Peverelli, E. Giardino, D. Treppiedi, M. Meregalli, M. Belicchi, V. Vaira, S. Corbetta, C. Verdelli, E. Verrua, A. L. Serban, M. Locatelli, G. Carrabba, G. Gaudenzi, E. Malchiodi, L. Cassinelli, A. G. Lania, S. Ferrero, S. Bosari, G. Vitale, Y. TorrenteA. Spada, G. Mantovani

Research output: Contribution to journalArticle

Abstract

The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05–14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p <0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.
Original languageEnglish
Pages (from-to)1870-1880
Number of pages11
JournalInternational Journal of Cancer
Volume140
Issue number8
DOIs
Publication statusPublished - Apr 15 2017

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Dopamine Receptors
Pituitary Neoplasms
Stem Cells
Cyclin D3
Cyclin-Dependent Kinase Inhibitor p27
Neoplasms
Dopamine Agents
somatostatin receptor 2
Gonadotropins
Carcinogenesis
Transcription Factors
Cell Proliferation
Pharmacology
Phenotype
Recurrence
Pharmaceutical Preparations

Keywords

  • dopamine
  • drug resistance
  • pituitary adenomas
  • somatostatin
  • tumor stem cells

Cite this

@article{9184995cdef04d19aa72afda84726241,
title = "Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors",
abstract = "The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70{\%} of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05–14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17{\%} and 35 ± 13{\%} inhibition, respectively, p <0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.",
keywords = "dopamine, drug resistance, pituitary adenomas, somatostatin, tumor stem cells",
author = "E. Peverelli and E. Giardino and D. Treppiedi and M. Meregalli and M. Belicchi and V. Vaira and S. Corbetta and C. Verdelli and E. Verrua and Serban, {A. L.} and M. Locatelli and G. Carrabba and G. Gaudenzi and E. Malchiodi and L. Cassinelli and Lania, {A. G.} and S. Ferrero and S. Bosari and G. Vitale and Y. Torrente and A. Spada and G. Mantovani",
year = "2017",
month = "4",
day = "15",
doi = "10.1002/ijc.30613",
language = "English",
volume = "140",
pages = "1870--1880",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors

AU - Peverelli, E.

AU - Giardino, E.

AU - Treppiedi, D.

AU - Meregalli, M.

AU - Belicchi, M.

AU - Vaira, V.

AU - Corbetta, S.

AU - Verdelli, C.

AU - Verrua, E.

AU - Serban, A. L.

AU - Locatelli, M.

AU - Carrabba, G.

AU - Gaudenzi, G.

AU - Malchiodi, E.

AU - Cassinelli, L.

AU - Lania, A. G.

AU - Ferrero, S.

AU - Bosari, S.

AU - Vitale, G.

AU - Torrente, Y.

AU - Spada, A.

AU - Mantovani, G.

PY - 2017/4/15

Y1 - 2017/4/15

N2 - The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05–14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p <0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.

AB - The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05–14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p <0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.

KW - dopamine

KW - drug resistance

KW - pituitary adenomas

KW - somatostatin

KW - tumor stem cells

U2 - 10.1002/ijc.30613

DO - 10.1002/ijc.30613

M3 - Article

VL - 140

SP - 1870

EP - 1880

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 8

ER -