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

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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.