Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells
Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication can...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1775 |
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| author | Corinne Iampietro Alessia Brossa Stefano Canosa Stefania Tritta Glenn E. Croston Torsten Michael Reinheimer Filippo Bonelli Andrea Roberto Carosso Gianluca Gennarelli Stefano Cosma Chiara Benedetto Alberto Revelli Benedetta Bussolati |
| author_facet | Corinne Iampietro Alessia Brossa Stefano Canosa Stefania Tritta Glenn E. Croston Torsten Michael Reinheimer Filippo Bonelli Andrea Roberto Carosso Gianluca Gennarelli Stefano Cosma Chiara Benedetto Alberto Revelli Benedetta Bussolati |
| author_sort | Corinne Iampietro |
| collection | DOAJ |
| description | Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment. |
| first_indexed | 2024-03-09T23:44:05Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:44:05Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-afd24dc39e1b4a5ba919ac70d90993c32023-11-23T16:46:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233177510.3390/ijms23031775Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal CellsCorinne Iampietro0Alessia Brossa1Stefano Canosa2Stefania Tritta3Glenn E. Croston4Torsten Michael Reinheimer5Filippo Bonelli6Andrea Roberto Carosso7Gianluca Gennarelli8Stefano Cosma9Chiara Benedetto10Alberto Revelli11Benedetta Bussolati12Department of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, ItalyEicOsis, Davis, CA 95616, USAReinheimer.Expert ApS, 2300 Copenhagen, DenmarkDepartment of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyObstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, ItalyEndometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment.https://www.mdpi.com/1422-0067/23/3/1775mesenchymal stromal cellsendometriosisquinagolidedopamine receptor agonistendothelial differentiationinvasion |
| spellingShingle | Corinne Iampietro Alessia Brossa Stefano Canosa Stefania Tritta Glenn E. Croston Torsten Michael Reinheimer Filippo Bonelli Andrea Roberto Carosso Gianluca Gennarelli Stefano Cosma Chiara Benedetto Alberto Revelli Benedetta Bussolati Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells International Journal of Molecular Sciences mesenchymal stromal cells endometriosis quinagolide dopamine receptor agonist endothelial differentiation invasion |
| title | Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells |
| title_full | Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells |
| title_fullStr | Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells |
| title_full_unstemmed | Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells |
| title_short | Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells |
| title_sort | quinagolide treatment reduces invasive and angiogenic properties of endometrial mesenchymal stromal cells |
| topic | mesenchymal stromal cells endometriosis quinagolide dopamine receptor agonist endothelial differentiation invasion |
| url | https://www.mdpi.com/1422-0067/23/3/1775 |
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