College of Pharmacy, Duksung Women's University, Seoul, Korea.
Proteomics. 2013 Nov;13(21):3145-56. doi: 10.1002/pmic.201300127. Epub 2013 Sep 24.
Early prediction of metastatic breast cancer is important for improvement of prognosis and survival rate. The present study aimed to identify secreted protein biomarkers for detection of invasive breast cancer. To this end, we performed a comparative proteomic analysis by a combination of 2DE and MALDI-TOF MS analysis of conditioned media from invasive H-Ras MCF10A human breast epithelial cells and noninvasive MCF10A and N-Ras MCF10A cells. We identified a list of 25 proteins that were strongly detected in media of H-Ras MCF10A and focused on annexin II, which was shown to be involved in cell motility. Invasive triple-negative human breast carcinoma cells, Hs578T, and MDA-MB-231, showed increased levels of annexin II in media, demonstrating that secretion of annexin II correlated well with the invasive phenotype of cells. We demonstrated a crucial role of annexin II in breast cell invasion/migration and actin cytoskeleton reorganization required for filopodia formation. Annexin II levels in the plasma samples and breast cancer tissues of breast cancer patients were significantly higher than those of normal groups, providing a clinical relevance to our in vitro findings. Taken together, we identified annexin II as a novel secretory biomarker candidate for invasive breast cancer, especially estrogen receptor-negative breast cancer.
早期预测转移性乳腺癌对于改善预后和生存率非常重要。本研究旨在鉴定用于检测浸润性乳腺癌的分泌蛋白生物标志物。为此，我们通过比较 2-DE 和 MALDI-TOF MS 分析侵袭性 H-Ras MCF10A 人乳腺上皮细胞和非侵袭性 MCF10A 和 N-Ras MCF10A 细胞的条件培养基，进行了蛋白质组学分析。我们鉴定了一组在 H-Ras MCF10A 培养基中强烈检测到的 25 种蛋白质，并集中研究了参与细胞运动的膜联蛋白 II。侵袭性三阴性人乳腺癌细胞 Hs578T 和 MDA-MB-231 在培养基中显示出膜联蛋白 II 水平升高，表明膜联蛋白 II 的分泌与细胞的侵袭表型密切相关。我们证明了膜联蛋白 II 在乳腺细胞侵袭/迁移和肌动蛋白细胞骨架重排中起着关键作用，这是形成丝状伪足所必需的。乳腺癌患者血浆样本和乳腺癌组织中的膜联蛋白 II 水平明显高于正常组，为我们的体外发现提供了临床相关性。总之，我们将膜联蛋白 II 鉴定为一种新型的浸润性乳腺癌，特别是雌激素受体阴性乳腺癌的分泌性生物标志物候选物。
