Research
BMP-2 signaling in ovarian cancer and its association with poor prognosis
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* Corresponding author: Anne-Marie Mes-Masson Anne-Marie.Mes-Masson@umontreal.ca
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
Journal of Ovarian Research 2009, 2:4 doi:10.1186/1757-2215-2-4
Published: 14 April 2009Abstract
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.