Tumor-associated lymphangiogenesis and its specific inhibition as a novel therapeutic strategy in malignant melanomas of the conjunctiva

肿瘤相关淋巴管生成及其特异性抑制作为结膜恶性黑色素瘤的新型治疗策略

• 批准号: 231383408
• 负责人: Dr. Jacobus J. Bosch
• 金额: --
• 依托单位: Zentrum für Augenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/231383408?language=en
• 关键词: Tumor; associated; lymphangiogenesis; its; specific

Malignant melanomas are the most common neoplasms of the eye and present with high mortality. Currently there is no effective therapy for prevention or treatment of conjunctival and uveal melanoma metastases. The outgrowth of new from preexisting lymphatic vessels (lymphangiogenesis) is considered as a decisive risk factor for metastasis and mortality of extraocular melanomas. Recently, we could demonstrate the presence of tumor-associated lymphangiogenesis in ocular melanomas, to our knowledge for the first time. These tumor-induced lymphatic vessels were significantly associated with an increased risk of local and systemic lymphatic spread, local recurrence and tumor-related death. In order to better understand the mechanisms of tumor-associated lymphangiogenesis, we are interested in analyzing the lymphangiogenic potency of melanoma cells and their interaction with lymphatic endothelial cells and prolymphangiogenc macrophages in vitro as well as in vivo. Furthermore, we will analyze whether and how tumor-associated lymphangiogenesis can modulate the immune response against melanoma cells. On this basis we will test in vivo the feasibility of the novel concept of reducing tumor metastasis by anti(lymph)angiogenic therapies in a mouse model of conjunctival melanoma. The medium-term aim is the clinical establishment of novel (neo)adjuvant anti(lymph)angiogenic therapies for malignant melanomas of the eye in order to improve tumor-specific survival of these patients.

恶性黑色素瘤是眼部最常见的肿瘤，死亡率高。目前还没有有效的治疗方法来预防或治疗结膜和葡萄膜黑色素瘤转移。眼外黑色素瘤转移和死亡的决定性危险因素是从原有的淋巴管（淋巴管生成）中生长出新的。最近，我们可以证明存在肿瘤相关的淋巴管生成在眼部黑色素瘤，我们的知识第一次。这些肿瘤诱导的淋巴管与局部和全身淋巴扩散、局部复发和肿瘤相关死亡的风险增加显著相关。为了更好地了解肿瘤相关淋巴管生成的机制，我们有兴趣在体外和体内分析黑色素瘤细胞的淋巴管生成能力及其与淋巴管内皮细胞和prolymphangiogenc巨噬细胞的相互作用。此外，我们将分析肿瘤相关的淋巴管生成是否以及如何调节对黑色素瘤细胞的免疫反应。在此基础上，我们将在结膜黑色素瘤小鼠模型中测试通过抗（淋巴）血管生成疗法减少肿瘤转移的新概念的体内可行性。中期目标是临床建立新的（新）辅助抗（淋巴）血管生成治疗眼睛恶性黑色素瘤，以提高这些患者的肿瘤特异性生存。