The chemokine crosstalk at the 'tumor-vessel interface'

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During tumor progression, malignant cells interact with stromal cells and modulate both hemangio- as well as lymphangiogenesis. Subsequently, intravasation of tumor cells starts a cascade finally leading to survival-limiting metastasis formation. These processes suggest bidirectional communication pathways guiding sprouting microvessels to tumors and instructing tumor cells to intravasate. To date, the underlying chemoattractive signals remain largely unknown. In the present project, we will investigate whether tumor cell-derived chemokines organize lymphangiogenesis and chemokines produced by lymphatic endothelial cells enable tumor cells to invade into lymphatic vessels initiating metastatic dissemination. To address these questions, we will take advantage of the scientific expertise within the SPP1190 consortium and use state of the art imaging tools, tumor models as well unique models of in vitro and in vivo lymphangiogenesis. Within the consortium, we will provide expertise on chemokines and their receptors, qPCR analysis of all known human and mouse chemokines/receptors, human immortalized blood and lymphatic microvascular endothelial cells, CCR6-, CCR8-, CCR9-deficient mice, neutralizing anti-chemokine and antichemokine receptor antibodies as well as chemokine receptor antagonists.