Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines

Paola Cassoni, Anna Sapino, Luca Munaron, Silvia Deaglio, Bice Chini, Andrea Graziani, Asif Ahmed, Gianni Bussolati

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Despite oxytocin receptors (OTR) being present in human choriodecidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [125I]oxytocin ([125I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH2 9]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.

Original languageEnglish
Pages (from-to)1130-1136
Number of pages7
JournalEndocrinology
Volume142
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

Oxytocin Receptors
Choriocarcinoma
Trophoblasts
Cell Proliferation
Cell Line
Proteins
Oxytocin
Protein-Tyrosine Kinases
Fluorescent Antibody Technique
Tyrosine
Binding Sites
Calcium
Polymerase Chain Reaction
Messenger RNA
Peptides
Growth
Neoplasms

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines. / Cassoni, Paola; Sapino, Anna; Munaron, Luca; Deaglio, Silvia; Chini, Bice; Graziani, Andrea; Ahmed, Asif; Bussolati, Gianni.

In: Endocrinology, Vol. 142, No. 3, 2001, p. 1130-1136.

Research output: Contribution to journalArticle

Cassoni, P, Sapino, A, Munaron, L, Deaglio, S, Chini, B, Graziani, A, Ahmed, A & Bussolati, G 2001, 'Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines', Endocrinology, vol. 142, no. 3, pp. 1130-1136. https://doi.org/10.1210/en.142.3.1130
Cassoni, Paola ; Sapino, Anna ; Munaron, Luca ; Deaglio, Silvia ; Chini, Bice ; Graziani, Andrea ; Ahmed, Asif ; Bussolati, Gianni. / Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines. In: Endocrinology. 2001 ; Vol. 142, No. 3. pp. 1130-1136.
@article{b008221475a64d0cae5a64cff20f16ff,
title = "Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines",
abstract = "Despite oxytocin receptors (OTR) being present in human choriodecidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [125I]oxytocin ([125I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH2 9]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.",
author = "Paola Cassoni and Anna Sapino and Luca Munaron and Silvia Deaglio and Bice Chini and Andrea Graziani and Asif Ahmed and Gianni Bussolati",
year = "2001",
doi = "10.1210/en.142.3.1130",
language = "English",
volume = "142",
pages = "1130--1136",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines

AU - Cassoni, Paola

AU - Sapino, Anna

AU - Munaron, Luca

AU - Deaglio, Silvia

AU - Chini, Bice

AU - Graziani, Andrea

AU - Ahmed, Asif

AU - Bussolati, Gianni

PY - 2001

Y1 - 2001

N2 - Despite oxytocin receptors (OTR) being present in human choriodecidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [125I]oxytocin ([125I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH2 9]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.

AB - Despite oxytocin receptors (OTR) being present in human choriodecidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [125I]oxytocin ([125I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH2 9]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.

UR - http://www.scopus.com/inward/record.url?scp=0035092586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035092586&partnerID=8YFLogxK

U2 - 10.1210/en.142.3.1130

DO - 10.1210/en.142.3.1130

M3 - Article

C2 - 11181528

AN - SCOPUS:0035092586

VL - 142

SP - 1130

EP - 1136

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 3

ER -