Cyr61 is a potential anti-angiogenic target for ovarian cancer therapy Free

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Background: Ovarian cancer accounts for more deaths in the United States than all other gynecologic cancers combined. Women with recurrent disease are considered incurable and palliative treatment is directed at improving quality-of-life. Biologic agent therapy is an especially attractive option. Anti-angiogenic drug development is a novel cancer treatment strategy that has generated widespread enthusiasm. Cysteine-rich 61 (Cyr61) is a secreted pro-angiogenic factor that has been shown to be transcriptionally activated by VEGF. Cyr61 is expressed at high levels in many human tumor types and found to promote cancer progression. Blockage of the Cyr61 pathway has been shown to suppress growth in vitro. However, the role of Cyr61 has not been previously studied in ovarian cancer. Methods: RNA and protein were extracted from ovarian cancer cell lines (n = 5), fresh-frozen human primary tumors (n = 10), normal ovarian surface epithelium cases (n = 2), and positive and negative controls (MCF7 and MDAMB231, respectively). The Cyr61 mRNA expression level was determined by RT-PCR using GAPDH as an internal control. Western blotting was performed by preparing lysates from the tissue specimens and visualizing immunoreactive bands. Results: Cyr61 mRNA was expressed in all samples. Western blot showed over-expression of Cyr61 protein in cell lines and primary tumors, but not in normal ovarian surface epithelium. Conclusions: Our results demonstrate that Cyr61 protein is over-expressed in ovarian cancers compared to the normal ovarian epithelium. However, no differences in mRNA levels could be detected between normal and tumor samples—suggesting post-transcriptional regulation. Cyr61 may be a promising target for anti-angiogenic ovarian cancer therapy.