BBB seminar: Michael Detmar
An important role of lymphatic vessels in cancer progression and inflammation
Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland
Our – originally controversial – concept that tumor-induced lymphangiogenesis promotes cancer metastasis to lymph nodes and likely beyond has today been generally accepted. Originally thought of as passive participants that provide increased drainage, tumor-associated lymphatic vessels likely play much more active roles in promoting cancer metastasis. Our recent studies, using new non-invasive near-infrared in vivo imaging techniques, indicate enhanced flow in tumor-associated and in inflammation-draining lymphatic vessels, as well as re-routing of lymphatic tumor drainage after sentinel lymph node metastasis. Tumor-associated lymphatic vessels also appear to inhibit the anti-tumoral immune response by several mechanisms. Tumor draining lymphatic vessels, as well as the expanded lymphatic vessels in tumor-draining lymph nodes (“lymph node lymphangiogenesis”), appear to provide a pre-metastatic niche for tumor cells and also a metastatic niche for cancer stem cells, as evidenced by the occurrence of in-transit metastasis and the persistence of cancer cells in lymph node sinuses. We have used several approaches to identify inhibitors of tumor-associated lymphangiogenesis, including phenotypic chemical genetics screens and development of recombinant soluble inhibitors. Our recent studies indicate that lymphatic endothelium, upon contact with cancer stem cells, secretes chemokines that promote the stemness of these cells that express the respective chemokine receptors. Lymphatic endothelium also plays an important role in chronic inflammatory diseases, and recent work from our laboratory, using novel activators of lymphatic function, indicates that activation of lymphatic endothelium reduces acute, immune- or ultraviolet B-induced inflammation, and also inhibits rheumatoid arthritis and chronic, psoriasis-like skin inflammation in experimental mouse models. Together, these findings reveal the lymphatic system as a new therapeutic target for treating advanced cancers and inflammatory diseases.
Chairperson: Helge Wiig, Department of Biomedicine