In-depth LC-MS/MS analysis of the chicken ovarian cancer proteome reveals conserved and novel differentially regulated proteins in humans

Abstract

Ovarian cancer (OVC) remains the most lethal gynecological malignancy in the world due to the combined lack of early-stage diagnostics and effective therapeutic strategies. The development and application of advanced proteomics technology and new experimental models has created unique opportunities for translational studies. In this study, we investigated the ovarian cancer proteome of the chicken, an emerging experimental model of OVC that develops ovarian tumors spontaneously. Matched plasma, ovary, and oviduct tissue biospecimens derived from healthy, early-stage OVC, and late-stage OVC birds were quantitatively characterized by label-free proteomics. Over 2600 proteins were identified in this study, 348 of which were differentially expressed by more than twofold (p≤0.05) in early- and late-stage ovarian tumor tissue specimens relative to healthy ovarian tissues. Several of the 348 proteins are known to be differentially regulated in human cancers including B2M, CLDN3, EPCAM, PIGR, S100A6, S100A9, S100A11, and TPD52. Of particular interest was ovostatin 2 (OVOS2), a novel 165-kDa protease inhibitor found to be strongly upregulated in chicken ovarian tumors (p=0.0005) and matched plasma (p=0.003). Indeed, RT-quantitative PCR and Western blot analysis demonstrated that OVOS2 mRNA and protein were also upregulated in multiple human OVC cell lines compared to normal ovarian epithelia (NOE) cells and immunohistochemical staining confirmed overexpression of OVOS2 in primary human ovarian cancers relative to non-cancerous tissues. Collectively, these data provide the first evidence for involvement of OVOS2 in the pathogenesis of both chicken and human ovarian cancer.

S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via the EGFR/Akt signaling pathway and E-cadherin

“…It mediates Ca 2+ -induced growth inhibition as well as stimulates growth by enhancing epidermal growth factor protein family members. 6,7 S100A11 is overexpressed in numerous cancers, including renal and papillary thyroid carcinomas, 8 colon cancer, 9 pancreatic cancer, 10 ovarian cancer, 11 and breast cancer. 12 How S100A11 influences renal carcinoma is unclear, so this was the focus of our investigation.…”

Enhanced Lipidome Coverage in Shotgun Analyses by using Gas-Phase Fractionation

“…The hen model is the only model for spontaneous development of ovarian cancer [30, 31], and has been the subject of proteomics and glycomics studies [32, 33]. Lipidomics investigations are crucial for systems-level approaches to investigate this model.…”

The PeptideAtlas of the Domestic Laying Hen

“…25 A subset of liver and ovary tissues were instead subjected to laser microdissection to isolate yolk, ovarian stroma, and follicular wall tissue, which were subsequently lysed in a buffer of 100 mM Tris-HCl, pH 7.5, 100 mM dithiothreitol (DTT), and 4% sodium dodecyl sulfate. 26 Plasma samples were used as collected.…”