EphA3-modulated cell positioning in tumour invasion and neovascularisation.

EphA3 调节细胞在肿瘤侵袭和新血管形成中的定位。

• 批准号: nhmrc : 384241
• 负责人: A/Pr Martin Lackmann
• 金额: $ 43.16万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/epha3-modulated-cell-invasion-neovascularisation/78296
• 关键词: EphA3; modulated; cell; positioning; tumour

During the progression of human cancers, tumor cells increasingly lose their ability to communicate and co-exist in a regulated fashion with normal cells to maintain the status quo. Because they multiply uncontrollably, tumour cells spread into surrounding tissue and can invade other organs of the body. The Ephs and interacting ephrins are proteins on the cell surface, and their communication controls the position of cells within the body tissues and organs, but also in tumours. Together with collaborators at the Ludwig Institute for Cancer Research and the Queensland Institute for Medical Research we produced two proteins, an antibody and a recombinant ephrin that bind one of the Eph proteins on tumour cells. The antibody allowed us to locate Eph in tumours, where it appears surprisingly not only on tumour cells but also on tumour blood vessels. When attached to a redioactive compund it selectively targets the cancer cells and in an animal study prolonged the survival of mice with leukemia significantly. We will now investigate the exact role of this Eph protein in tumour blood vessels. We will then study what happens in tumours when a toxic antibody-drug compound targets this tumour and starts to kill tumour cells. Finally, we will devise a novel reagent that combines the properties of the antibody with the properties of the ephrin into a single protein, which can deliver a cell-killing drug exclusively and most efficiently to tumour cells containing the Eph protein on its surface.

在人类癌症的发展过程中，肿瘤细胞逐渐失去与正常细胞沟通和共存的能力，以一种受调节的方式维持现状。由于它们的繁殖不受控制，肿瘤细胞会扩散到周围的组织中，并可能侵入身体的其他器官。Ephs和相互作用的ephrin是细胞表面的蛋白质，它们之间的交流控制着细胞在身体组织和器官中的位置，也控制着肿瘤中的位置。与路德维希癌症研究所和昆士兰医学研究所的合作者一起，我们生产了两种蛋白质，一种抗体和一种重组ephrin，它们与肿瘤细胞上的一种Eph蛋白结合。这种抗体使我们能够定位肿瘤中的Eph，令人惊讶的是，它不仅出现在肿瘤细胞上，而且出现在肿瘤血管上。当与一种放射性化合物结合时，它会选择性地靶向癌细胞，在一项动物研究中，它显著延长了白血病小鼠的存活时间。我们现在将研究这种Eph蛋白在肿瘤血管中的确切作用。然后，我们将研究当一种有毒的抗体药物化合物靶向肿瘤并开始杀死肿瘤细胞时，肿瘤中会发生什么。最后，我们将设计一种新的试剂，将抗体的特性与ephrin的特性结合成一种单一的蛋白质，这种蛋白质可以最有效地向表面含有Eph蛋白的肿瘤细胞提供细胞杀伤药物。