Sorafenib inhibits growth, migration, and angiogenic potential of ectopic endometrial mesenchymal stem cells derived from patients with endometriosis

Moggio A, Aldo Moggio, Pittatore G, Giulia Pittatore, Paola Cassoni, Cassoni P, Gian Luigi Marchino, Marchino Gl, Alberto Revelli, Benedetta Bussolati
Fertility and sterility · 2012 · vol. 98(6) , pp. 1521–1530.e2 · doi:10.1016/j.fertnstert.2012.08.003 · PMID:22981172 · W1980359106
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Sorafenib treatment reduced the growth, migration, and angiogenic potential of endometrial mesenchymal stem cells isolated from endometriosis patients.

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Abstract

ObjectiveTo characterize the proliferation, migration, and angiogenic properties of mesenchymal stem cells (MSC) from ectopic and eutopic endometrial tissue and to investigate the effect of the tyrosine kinase inhibitor sorafenib.DesignIn vitro studies.SettingUniversity hospital and research center.Patient(s)Patients receiving surgical treatment of endometriosis (n = 4) and control patients without endometriosis (n = 2) undergoing surgery for benign gynecologic diseases.Intervention(s)Mesenchymal stem cell lines were isolated from ectopic and eutopic endometrial tissue, and sorafenib was administered to them.Main outcome measure(s)Proliferation, migration, invasion of endometrial MSC, and expression of ezrin, vascular endothelial growth factor, and hypoxia-inducible factor-1α (HIF-1α) were measured.Result(s)Ectopic endometrial MSC from patients with endometriosis showed a higher proliferation, migration, and angiogenic ability than eutopic MSC from the same patient or control MSC from patients without endometriosis. Sorafenib reduced the proliferation, motility, ezrin phosphorylation, vascular endothelial growth factor release, and HIF-1α expression of ectopic MSC.Conclusion(s)The increased proliferative, migratory, and angiogenic phenotype of ectopic MSC may be reverted by treatment with sorafenib. Targeting of the MSC population involved in sustaining the ectopic lesions might be useful in eradicating endometriotic implants.

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Condition tags

endometriosis

MeSH descriptors

Benzenesulfonates Endometriosis Endometriosis Endometrium Mesenchymal Stem Cells Neovascularization, Pathologic Neovascularization, Pathologic Pyridines Adult Angiogenesis Inhibitors Angiogenesis Inhibitors Benzenesulfonates Cell Movement Cell Movement Cell Proliferation Cell Proliferation Cells, Cultured Endometriosis Endometrium Endometrium

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