黑色素瘤干细胞调节肿瘤转移的细胞及分子机制研究

项目名称： 黑色素瘤干细胞调节肿瘤转移的细胞及分子机制研究

项目编号： No.81472671

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 马捷

作者单位： 复旦大学

项目金额： 72万元

中文摘要： 早期转移是黑色素瘤预后差的主要原因。黑色素瘤干细胞推动肿瘤的持续生长，是影响黑色素瘤转移的关键因素，但其调节肿瘤转移的机制尚不清除。我们前期研究发现作为黑色素瘤干细胞分子标记的ABCB5基因在功能上参与黑色素瘤转移，整合素在ABCB5基因调节肿瘤细胞迁徙的过程中发挥重要作用。本课题拟在前期研究基础上，通过遗传标记揭示肿瘤干细胞谱系在转移病灶中的功能，明确靶向清除肿瘤干细胞对转移病灶的影响；利用基因敲除小鼠及人源肿瘤细胞移植模型，验证ABCB5基因在肿瘤转移中的作用；通过分析ABCB5基因对细胞粘附、侵袭、细胞间通讯等环节的影响，阐明黑色素瘤干细胞通过ABCB5基因调节肿瘤转移的干性机制。本研究发现将为揭示黑色素瘤转移机制、开发更为有效的转移病灶检测及治疗方法提供科学依据。

中文关键词： C20_皮肤及黑色素瘤；肿瘤干细胞；肿瘤转移；ABCB5

英文摘要： Metastasis often occurs at early stage of melanoma disease progression and contributes to the poor prognosis associated with this malignant disease. Melanoma stem cell is the driving force behind sustained tumor grwoth, and plays a critical role in metastatic melanoma progression. However, the mechanism of melanoma stem cell-regulated tumor metastasis remains unknown. Our previous studies revealed that melanoma stem cell marker ABCB5 is functionally involved in melanoma metastasis, in which integrin plays an important role in tumor cell dissemination. In this project, we will investigate the role of melanoma stem cells in tumor metastasis through lineage tracking and depletion. The function of the ABCB5 gene in melanoma metastasis will be determined by using both the Abcb5 gene knockout mouse model and human melanoma xenotransplatation model. The molecular mechanism of melanoma stem cell-regulated tumor metastasis will be further investigated, with a focus on the regulation of cell adhesion, invasion and cell-cell communication by the ABCB5 gene. The findings of these studies will help to reveal the mechanism of metastatic melanoma pathogenesis, and provide scientific evidences for the development of novel approaches for melanoma diagnosis and treatment.

英文关键词： Melanoma;Cancer stem cells;Metastasis;ABCB5