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

Capsule:
Ectopic endometrial mesenchymal stem cells (MSC) show increased proliferation, migration, vascular endothelial growth factor release, and HIF-1a expression in respect to eutopic or control MSC. Sorafenib inhibits both functional properties and angiogenic phenotype.

Authors:
Aldo Moggio, M.Sc., Giulia Pittatore, M.D., Paola Cassoni, M.D., Ph.D., Gian Luigi Marchino, M.D., Alberto Revelli, M.D., Ph.D., Benedetta Bussolati1, M.D., Ph.D.

Volume 98, Issue 6, Pages 1521-1530.e2, December 2012

Abstract:

Objective:
To 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.

Design:
In vitro studies.

Setting:
University hospital and research center.

Patients:
Patients receiving surgical treatment of endometriosis (n=4) and control patients without endometriosis (n=2) undergoing surgery for benign gynaecological diseases.

Intervention:
MSC lines were isolated from ectopic and eutopic endometrial tissue and Sorafenib was administered to them.

Main Outcome Measure:
Proliferation, migration, invasion of endometrial MSC, and expression of ezrin, vascular endothelial growth factor, and hypoxia-inducible factor-1α (HIF-1α) were measured.

Results:
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, VEGF release and HIF-1α expression of ectopic MSC.

Conclusions:
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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