Epithelial ovarian cancer is the most lethal gynecologic
cancer with a 5 years survival rate of 30-40% in patients diagnosed with high-grade invasive disease (TOV). This is in stark contrast to the 95% 5 years survival rate in
ovarian cancer patients diagnosed with low malignant potential (LMP) disease. The progression from localized
tumor to invasive
metastasis involves matrix proteolysis.
Protease inhibitors are thought to play a key role by limiting this process. Using the Affymetrix HG-U133A GeneChip array, we have studied all
serine protease inhibitors and found several
serpin family members that are differentially expressed between LMP and TOV serous
tumors. SERPINA1 was selected for further study due to its high expression in the majority of LMP
tumors and its low expression in TOV
tumors; observations that were also validated by quantitative-PCR (Q-PCR). To study the effects of its over expression on different tumorigenic parameters, SERPINA1 was cloned in the pcDNA3.1+ plasmid which was subsequently used to derive stable clones from two invasive
ovarian cancer cell lines, TOV-112D and TOV-1946. We found no effect of SERPINA1 over expression on
tumor growth in SCID mice although cell migration and invasion were affected in in vitro assays. There was also no association between patient survival and SERPINA1 immunostaining, however, SERPINA1 localization was different in LMP (nuclear) and TOV (cytoplasmic)
tumors. SERPINA1 remains an interesting candidate since protein homeostasis, regulated by
proteases and their inhibitors, should be studied holistically in order to assess their full impact in
tumor progression.