The importance of VEGF-D, an angiogenic protein, for lymphangiogenesis, tumor growth and metastasis.

肿瘤通过吸引血管来获取生长所需的营养物质。此外，肿瘤中血管的存在使肿瘤细胞能够进入血液并扩散到身体的远处--这一过程被称为转移，是癌症患者死亡的主要原因。血管的生长--血管生成--是肿瘤吸引血管生成的机制。阻断肿瘤血管生成的能力将在临床上有很大的好处，因为它将限制肿瘤的生长和扩散。肿瘤细胞通过分泌血管生成生长因子来吸引血管，这些生长因子可以刺激内皮细胞的增殖，内皮细胞是构成血管内层的细胞。这些血管内皮生长因子(VEGFs)是蛋白质。我们在路德维希癌症研究所墨尔本分院的实验室发现了一种血管内皮生长因子，即血管内皮生长因子-D。血管内皮生长因子-D刺激血管的生长，可能还有淋巴管的生长，存在于最常见的人类癌症中，包括恶性黑色素瘤、乳腺癌和肺癌。我们假设某些肿瘤的血管生成依赖于血管内皮生长因子-D。此外，肿瘤细胞分泌的血管内皮生长因子-D可能刺激淋巴管的生长-淋巴管的生成。由于转移常通过淋巴管扩散，血管内皮生长因子-D诱导的肿瘤淋巴管生成可能参与了转移的发生。本研究的目的是确定血管内皮生长因子D在肿瘤血管生成和淋巴管生成中的作用。首先，我们将深入研究血管内皮生长因子-D在人类肿瘤中的定位。其次，我们将检测血管内皮生长因子-D的淋巴管生成活性。第三，分析过表达血管内皮生长因子-D的肿瘤在小鼠体内的生长和转移扩散情况。最后，将研究血管内皮生长因子-D的生物化学和基因调控方面，以开发抑制血管内皮生长因子-D在癌症中的作用的策略。

Tumors attract blood vessels to obtain the nutrients for growth. Furthermore, the presence of blood vessels in a tumor enables tumor cells to enter the bloodstream and spread to distant parts of the body - a process known as metastatis that is the major cause of death in cancer patients. The growth of blood vessels - angiogenesis - is the mechanism by which tumors attract the vasculature. The capacity to block tumor angiogenesis would be of great benefit in the clinic as it would restrict both the growth and spread of tumors. Tumor cells attract blood vessels by secreting angiogenic growth factors that stimulate the proliferation of endothelial cells - the cells that form the inner lining of blood vessels. These Vascular Endothelial Growth Factors (VEGFs) are proteins. One VEGF, namely VEGF-D, was discovered in our laboratory at the Melbourne Branch of the Ludwig Institute for Cancer Research. VEGF-D stimulates the growth of blood vessels and possibly lymphatic vessels and is present in the most common human cancers including malignant melanoma and cancer of the breast and lung. We hypothesize that angiogenesis in some tumors is dependent on VEGF-D. Moreover, VEGF-D secreted by tumor cells may stimulate growth of lymphatic vessels - lymphangiogenesis. As metastatic spread often occurs via the lymphatic vessels, tumor lymphangiogenesis induced by VEGF-D may contribute to metastasis. The purpose of the research project is to determine the role of VEGF-D in tumor angiogenesis and lymphangiogenesis. Firstly we will thoroughly characterize the localization of VEGF-D in human cancer. Secondly, we will test VEGF-D for lymphangiogenic activity. Thirdly, the growth and metastatic spread in mice of tumors overexpressing VEGF-D will be analysed. Finally, aspects of VEGF-D biochemistry and gene regulation will be studied to develop strategies for inhibition of VEGF-D action in cancer.