Project Details
Projekt
The role of midkine in tumor-associated lymphangiogenesis and metastasis of ocular malignant melanoma.
Applicants
Dr. Jacobus J. Bosch; Professor Dr. Ludwig M. Heindl
Subject Area
Ophthalmology
Term
from 2015 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 257498687
Malignant melanoma is the most frequent cancer of the eye. Despite availability of effective treatment options for primary conjunctival and uveal melanoma, none of these therapies prevent development of metastases and to date there is no therapy that increases survival in metastastic conjunctival and uveal melanoma of the eye. Previously, we identified that outgrowth of new lymphatic vessels from preexisting ones (lymphangiogenesis) is a decisive risk factor for metastatic spread and an indicator of poor prognosis in ocular melanoma. In the first funding period, we investigated the underlying cellular and molecular mechanisms both in vitro and in vivo in a novel mouse model of conjunctival melanoma. This led us to identify midkine as a key cytokine in tumor-associated lymphangiogenesis, immune cell infiltration and metastasis in uveal and conjunctival melanoma.In the second funding period, we plan to study in depth the molecular signaling mechanisms and cellular function of midkine in ocular melanoma. Specifically, we will focus on the role of midkine in ocular melanoma-associated lympangiogenesis and metastasis both in vitro and in vivo. In addition, the role of midkine in the tumormicroenvironment, specifically tumor cell-stroma interaction via lymphatic endothelial cells and infiltration of tumor-associated macrophages will be addressed. Based on these findings we will explore whether targeting midkine could be a novel anti-(lymph)angiogenic therapy for attenuation of tumor metastasis and recurrence in our novel mouse model of metastatic conjunctival melanoma.
DFG Programme
Research Units
