Research

BMP-2 signaling in ovarian cancer and its association with poor prognosis

Cécile Le Page¹ , Marie-Line Puiffe¹ , Liliane Meunier¹ , Magdalena Zietarska¹ , Manon de Ladurantaye¹ , Patricia N Tonin^2,3 , Diane Provencher^1,4 and Anne-Marie Mes-Masson^1,5

¹  Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR/CHUM)/Institut du cancer de Montréal, Montréal, Canada

²  Departments of Human Genetics and Medicine, McGill University, Canada

³  The Research Institute of the McGill University Health Centre, Montréal, Canada

⁴  Départment de gynécologie et obstétrique, Université de Montréal, Montreal, QC, Canada

⁵  Départment de Médicine, Université de Montréal, Montréal, Montréal, Canada

author email corresponding author email

Journal of Ovarian Research 2009, 2:4doi:10.1186/1757-2215-2-4

Published:	14 April 2009

Abstract

Background

We previously observed the over-expression of BMP-2 in primary cultures of epithelial ovarian cancer (EOC) cells as compared to normal epithelial cells based on Affymetrix microarray profiling [1]. Here we investigate the effect of BMP-2 on several parameters of ovarian cancer tumorigenesis using the TOV-2223, TOV-1946 and TOV-112D EOC cell lines.

Methods

We treated each EOC cell line with recombinant BMP-2 and assayed various parameters associated with tumorigenesis. More specifically, cell signaling events induced by BMP-2 treatment were investigated by western-blot using anti-phosphospecific antibodies. Induction of Id1, Snail and Smad6 mRNA expression was investigated by real time RT-PCR. The ability of cells to migrate was tested using the scratch assay. Cell-cell adhesion was analyzed by the ability of cells to form spheroids. We also investigated BMP-2 expression in tissue samples from a series of EOC patients.

Results

Treatment of these cell lines with recombinant BMP-2 induced a rapid phosphorylation of Smad1/5/8 and Erk MAPKs. Increased expression of Id1, Smad6 and Snail mRNAs was also observed. Only in the TOV-2223 cell line were these signaling events accompanied by an alteration in cell proliferation. We also observed that BMP-2 efficiently increased the motility of all three cell lines. In contrast, BMP-2 treatment decreased the ability of TOV-1946 and TOV-112D cell lines to form spheroids indicating an inhibition of cell-cell adhesion. The expression of BMP-2 in tumor tissues from patients was inversely correlated with survival.

Conclusion

These results suggest that EOC cell secretion of BMP-2 in the tumor environment contributes to a modification of tumor cell behavior through a change in motility and adherence. We also show that BMP-2 expression in tumor tissues is associated with a poorer prognosis for ovarian cancer patients.