项目名称: 促炎分子cPLA2a调控乳腺癌转移的作用及机制研究
项目编号: No.81201646
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 肿瘤学1
项目作者: 郭华
作者单位: 天津医科大学
项目金额: 23万元
中文摘要: 侵袭和转移是恶性肿瘤的基本特征,也是根治恶性肿瘤的最大障碍。研究表明,肿瘤相关性炎症在肿瘤侵袭和转移中具有重要的作用。免疫学研究显示,磷脂水解酶cPLA2α是一个促炎信号分子。我们在前期研究中发现cPLA2α在乳腺癌组织中高表达,与淋巴结转移和C-erbB-2表达阳性密切相关,抑制cPLA2α表达后能够明显抑制表皮生长因子诱导的乳腺癌细胞的趋化运动能力。因此我们推测促炎信号分子cPLA2α在肿瘤细胞的移行、侵袭和转移中具有重要作用。为证实此假设本项目拟在前期基础上,通过体外细胞学实验、免疫缺陷小鼠模型及病人样本进一步探讨cPLA2α对调控癌细胞迁移和粘附的分子机制,以及在肿瘤转移中的功能,探索其作为治疗肿瘤转移药物靶点的潜在可能性。本研究预期结果将为控制上皮组织来源的恶性实体瘤细胞转移提供理论依据,同时揭示炎症与肿瘤发生转移可能共享cPLA2α信号分子。
中文关键词: 胞浆型磷脂酶A2a;上皮-间充质转化;肿瘤干细胞;转移;异质性
英文摘要: Invasion and metastasis are the basic characteristics of malignant tumors, and the biggest obstacle to cure malignant tumors. Studies have suggested that tumor-related inflammation plays an important role in tumorigenesis, progression and metastasis. In preliminary studies, our results have shown that a pro-inflammatory molecule cPLA2α highly expressed in the breast cancer tissues,and its expression is closely related to lymph node metastasis and positive expression of C-erB-2. Inhibition of the cPLA2α expression inhibits chemotaxis of breast cancer cells. Thus, we hypothesize that cPLA2α, a pro-inflammatory signaling molecule, plays an important role in cancer cell migration, invasion and metastasis. To test this hypothesis, we will investigate the molecular mechanism of cPLA2α-mediated cancer cell migration, the role of cPLA2α in metastasis by a SCID mouse model, and the association of cPLA2α expression with tumorigenesis and metastasis in patient samples. The expected results of this study will provide a theoretical basis for control of malignant solid tumor of epithelial tissue origin, and disclose that inflammation and tumorgenesis may share the common cPLA2α signaling pathway.
英文关键词: cytosolic phospholipase A2a;epithelial-mesenchymal transition;cancer stem cells;metastasis;heterogeneity