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

VEGF-D（一种血管生成蛋白）对于淋巴管生成、肿瘤生长和转移的重要性。

• 批准号: nhmrc : 164800
• 负责人: Prof Marc Achen
• 金额: $ 15.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/importance-vegf-d-growth-metastasis/94388
• 关键词: importance; VEGF; angiogenic; protein; lymphangiogenesis

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.

肿瘤吸引血管以获得生长所需的营养。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端部位-这一过程称为转移，是癌症患者死亡的主要原因。血管的生长--血管生成--是肿瘤吸引脉管系统的机制。阻断肿瘤血管生成的能力在临床上将是非常有益的，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，这些生长因子刺激内皮细胞的增殖，内皮细胞形成血管的内层。这些血管内皮生长因子（VEGF）是蛋白质。我们在路德维希癌症研究所墨尔本分支的实验室发现了一种VEGF，即VEGF-D。VEGF-D刺激血管和可能的淋巴管的生长，并且存在于最常见的人类癌症中，包括恶性黑色素瘤以及乳腺癌和肺癌。我们假设，在某些肿瘤血管生成是依赖于VEGF-D。此外，由肿瘤细胞分泌的VEGF-D可刺激淋巴管的生长-淋巴管生成。由于转移性扩散通常通过淋巴管发生，VEGF-D诱导的肿瘤淋巴管生成可能有助于转移。该研究项目的目的是确定VEGF-D在肿瘤血管生成和淋巴管生成中的作用。首先，我们将彻底表征VEGF-D在人类癌症中的定位。其次，我们将测试VEGF-D的淋巴管生成活性。第三，将分析过表达VEGF-D的肿瘤在小鼠中的生长和转移扩散。最后，将研究VEGF-D生物化学和基因调控方面，以开发抑制VEGF-D在癌症中作用的策略。