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Chordin is underexpressed in ovarian tumors and reduces tumor cell motility

F. Moll^*,1, C. Millet^,1, D. Noël, B. Orsetti, A. Bardin^||, D. Katsaros^¶, C. Jorgensen, M. Garcia^||, C. Theillet, P. Pujol^|| and V. François^**,2

^* Max-Planck-Institut für Biochemie, Martinsried bei München, Germany;
LCMB NIH/NCI, Bethesda, Maryland, USA;
Immunopathologie des maladies tumorales et auto-immunes, INSERM U475, Montpellier, France;
EMI 229 INSERM Génotypes et Phénotypes Tumoraux, CRLC Val d’Aurelle, Montpellier, France;
^|| Endocrinologie Moléculaire et Cellulaire des Cancers, INSERM U540, Montpellier, France;
^¶ Gynaecologic Oncology and Breast Cancer Unit, University of Torino School Medicine, Italy; and
^** Institut de Génétique Humaine, CNRS-UPR1142, Montpellier, France

² Correspondence: Institut de Génétique Humaine, CNRS-UPR1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. E-mail: vincent.francois{at}igh.cnrs.fr

Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.—Moll, F., Millet, C., Noël, D., Orsetti, B., Bardin, A., Katsaros, D., Jorgensen, C., Garcia, M., Theillet, C., Pujol, P., and François V.

Key Words: ovarian carcinoma • BMP antagonist

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