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Mol. Hum. Reprod. Advance Access published online on March 11, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah162
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received September 27, 2004
Accepted November 9, 2004

Article

The macrophage stimulating protein/RON system: a potential novel target for prevention and treatment of endometriosis

S. Matsuzaki 1*, M. Canis 2, J.L. Pouly 2, P. Dechelotte 3, K. Okamura 4, and G. Mage 2

1 Department of Gynecology, Polyclinique de l'Hôtel-Dieu, CHU, Clermont-Ferrand, France, Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan and
2 Department of Gynecology, Polyclinique de l'Hôtel-Dieu, CHU, Clermont-Ferrand, France
3 Department of Pathology, Hôtel-Dieu, CHU, Clermont-Ferrand, France
4 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan and

* To whom correspondence should be addressed.
S. Matsuzaki, E-mail: sachikoma{at}aol.com


  Abstract

Our recent DNA microarray analysis using tissue obtained by laser capture microdissection (LCM) identified up-regulation of RON (a tyrosine kinase receptor) during the late secretory phase in eutopic endometrial epithelial cells from patients with deep endometriosis compared with control endometrium from women with macroscopically normal pelvic cavities. In the present study, we further investigated mRNA expression of RON and its ligand, macrophage stimulating protein (MSP), in deep endometriotic lesions, eutopic endometrium from patients with deep endometriosis and control endometrium by using LCM and quantitative real-time RT-PCR. MSP mRNA expression in endometrial epithelial cells was significantly up-regulated in endometriosis patients during the late secretory phase compared with expression in controls. Furthermore, we detected up-regulation of MSP mRNA in ectopic endometrial epithelial cells compared with matched eutopic endometrial epithelial cells within the same patients regardless of the menstrual phase. MSP has an intrinsically dual functional nature through its receptor RON--it is a trophic cytokine preventing apoptosis and a scatter factor promoting invasion, both of which may be necessary for the initial development and growth of endometriosis. The present findings suggest that the MSP/RON system may be involved in the pathophysiology of endometriosis.

Keywords: endometriosis; endometrium; laser capture microdissection; macrophage stimulating protein; RON.
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