Effects of HLEC on the secreted proteins of epithelial ovarian cancer cells prone to metastasize to lymph nodes

• Published in: Cancer biology & medicine 2013-12, Vol.10 (4), p.221-226
• Main Authors: Zhang, Xin-Ying, Yin, Fu-Qiang, Liu, Li, Gao, Ting, Ruan, He-Yun, Guan, Xiao, Lu, Ying-Xin, Li, Dan-Rong
• Format: Article
• Language: English
• Subjects: Bioinformatics; Cell culture; Cell growth; Cytokines; Down-regulation; ELISA检测; Enzyme-linked immunosorbent assay; human lymphatic capillary endothelial cells; IGFBP; Lymph nodes; lymphatic metastasis; Lymphatic system; Mass spectroscopy; Metastases; Metastasis; Original; Osteonectin; Ovarian cancer; Polypeptides; Proteins; Quantitative analysis; secreted proteins; Signal transduction; Software; SPARC; Studies; tumor microenvironment; Tumors; Vascular endothelial growth factor; 上皮; 分泌蛋白; 卵巢癌细胞; 淋巴结肿大; 生物信息学
• ISSN: 2095-3941; 2095-3941
• DOI: 10.7497/j.issn.2095-3941.2013.04.006

Objective： To study explores the effect of HLEC on the secreted proteins of epithelial ovarian cancer （EOC） cells （SKOV3-PM4） with directional highly lymphatic metastasis. Methods： Supernatants of four groups of cultured cells, namely, SKOV3 （A）, SKOV3＋HLEC （B）, SKOV3-PM4 （C）, SKOV3-PM4＋HLEC （D）, were collected, and their proteins were detected by antibody arrays and iTRAOcZD-LC-MALDI- TOF/TOF/MS. Significantly differential proteins were further analyzed via bioinformatics and validated in human serums and cell media via ELISA. Results： Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA were upregulated in group C （compared with group A）, whereas IGFBP7 and SPARC were downregulated in group D （compared with group C）. Comprehensive bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked to each other. Further validation with serums showed statistical significance in VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign tumors, and control groups. Two proteins were upegulated in the first group. VEGFA in the control group was downregulated. For IGFBP, upregulation in the control group and down-regulation in the first group were also observed. Conclusion： The HLEC microenvironment is closely associated with directional metastasis to lymph nodes and with differential proteins including cell stromal proteins and adhesion factors. The upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 are closely associated with directional metastasis to lymph nodes in EOC cells.