EphA3-modulated cell positioning in tumour invasion and neovascularisation.

在人类癌症的发展过程中，肿瘤细胞越来越失去沟通的能力，并以受调控的方式与正常细胞共存，以维持现状。由于肿瘤细胞无法控制地繁殖，它们会扩散到周围组织，并可能侵袭身体的其他器官。Ephs和相互作用的肾上腺素是细胞表面的蛋白质，它们的通讯控制细胞在体内组织和器官中的位置，也控制肿瘤中的位置。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，一种抗体和一种将其中一种Eph蛋白结合到肿瘤细胞上的重组ePhin。这种抗体使我们能够在肿瘤中定位Eph，令人惊讶的是，它不仅出现在肿瘤细胞上，还出现在肿瘤血管上。当与放射性化合物结合时，它选择性地靶向癌细胞，并在动物研究中显着延长白血病小鼠的存活期。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，将抗体的特性和Ephin的特性结合到单一蛋白质中，它可以将一种细胞杀伤药物专门和最有效地输送到表面含有Eph蛋白的肿瘤细胞中。

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.