Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells

International Journal of Molecular Sciences

Stefania Tritta¹  Alessia Brossa¹  Corinne Iampietro¹  Filippo Bonelli¹  Benedetta Bussolati¹  Glenn E. Croston²  Stefano Cosma³  Andrea Roberto Carosso³  Stefano Canosa³  Chiara Benedetto³  Gianluca Gennarelli³  Alberto Revelli³  Torsten Michael Reinheimer⁴ 

[1] Department of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, 10126 Torino, Italy;EicOsis, Davis, CA 95616, USA;Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, Department of Surgical Sciences, Università degli Studi di Torino, 10126 Torino, Italy;Reinheimer.Expert ApS, 2300 Copenhagen, Denmark;

关键词: mesenchymal stromal cells;    endometriosis;    quinagolide;    dopamine receptor agonist;    endothelial differentiation;    invasion;   

DOI  :  10.3390/ijms23031775

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown