Lymphangiogenesis and cancer

• Applicant: Professor Dr. Jonathan Paul Sleeman
• Subject Area: Pathology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22033752

Tumor-induced lymphangiogenesis has emerged as an important driving force behind the entry of tumor cells into the lymphatics and subsequent metastasis formation in lymph nodes. VEGFR-3 activation on lymphatic endothelial cells in response to VEGF-C and VEGF-D produced by tumors plays a central role in regulating this process. VEGFR-3 therefore represents a promising target for cancer therapies aimed at suppressing metastasis. However, other pro-lymphangiogenic factors are also produced by tumors, and these may also make a contribution to tumor-induced lymphangiogeneis. We therefore propose to explore the relative contribution of these prolymphangiogenic factors to tumor-induced lymphangiogenesis and metastasis. We also plan to investigate the effects of tumor-produced degradation products of hyaluronate on the lymphatic endothelium, and to determine whether these contribute to tumor-induced lymphangiogenesis and metastasis. Therapies directed against tumor-induced lymphangiogenesis will only be effective if they inhibit not only metastasis to lymph nodes but also to vital organs. Thus we also plan to genetically mark all tumor cells that enter the lymphatic system from the primary tumor, then to assess their relative contribution to metastasis formation in vital organs in comparison to tumor cells that have only circulated in the blood.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1190: The Tumour-Vessel Interface