Cisplatin-Induced Changes in Proteomic Profiles of Ovarian Cancer Cell and HaCaT Secretomes

Exogenous signals from drug-stressed cancer cells promote acquisition of a more aggressive phenotype of neighboring tumor cells. To identify extracellular signaling molecules that potentially contribute to the development of therapy resistance, we examined how cancer cell secretome changes in response to chemotherapy. We performed LC-MS/MS analysis of secretomes from several ovarian cancer cell lines representing different tumor subtypes: serous ovarian cancer cell line (OVCAR3), ovarian cystadenocarcinoma cell line (MESOV) and clear cell ovarian cancer primary culture isolated from ascites (cells 26) before and 48 hours after cisplatin treatment. In addition, we studied secretomes from keratinocyte-derived epithelial cell line HaCaT as non-cancerous “normal” cells. Functional annotation of proteins which secretion increased after cisplatin showed that these proteins were mainly associated with cluster of spliceosome.

药物应激肿瘤细胞所释放的外源性信号，可促进邻近肿瘤细胞获得更强的侵袭表型。为筛选可能参与治疗耐药发生的细胞外信号分子，我们探究了肿瘤细胞分泌组（secretome）在化疗刺激下的变化情况。我们针对数株代表不同肿瘤亚型的卵巢癌细胞系的分泌组开展了液相色谱-串联质谱（LC-MS/MS）分析：包括浆液性卵巢癌细胞系OVCAR3、卵巢囊腺癌细胞系MESOV，以及从腹水中分离获得的透明细胞卵巢癌原代培养细胞（26号细胞），分别在顺铂处理前及处理48小时后进行检测。此外，我们还以角质形成细胞来源的上皮细胞系HaCaT作为非癌性“正常”细胞，对其分泌组进行了分析。对顺铂处理后分泌水平上调的蛋白质进行功能注释后发现，这些蛋白主要与剪接体簇相关。