BBB Seminar: Jonathan P. Sleeman
The contribution of the lymphatic system to metastatic spread
Jonathan P. Sleeman
Center for Biomedicine and Medical Technology Mannheim (CBTM), University of Heidelberg, and Karlsruhe Institute of Technology (KIT), Germany
The role of the lymphatic system in determining the formation of metastases in vital organs continues to be debated. On the one hand, for many types of tumors the presence of lymph node metastases is a strong indicator of poor prognosis, yet on the other hand recent clinical trials provide little evidence that surgical removal of lymph nodes has any therapeutic benefit. Pro-lymphangiogenic factors produced by tumors can induce lymphangiogenesis within and / or at the periphery of tumors, and can promote metastasis. This tumor-induced lymphangiogenesis is thought to act by promoting the entry of tumor cells into the lymphatic vasculature, and / or by increasing interstitial fluid flow to the draining lymph nodes, thereby facilitating their access to and entry into the regional nodes. In addition to classical growth factor-mediated lymphangiogenesis, we have found that hyaluronan oligosaccharides that accumulate in tumors also affect tumor-associated lymphatics. Although pro-lymphangiogenic factors are produced in the primary tumor environment, there is mounting evidence to suggest that they may act systemically in addition to their local effects on the tumor-associated lymphatics. Furthermore, we have found that the microenvironment of the lymph node conditions tumor cells and endows them with a number of properties associated with enhanced metastatic potential. Thus the interaction between tumor cells and the microenvironment offered by the lymphatic system contributes to metastasis formation at a number of different levels.
Host: Helge Wiig, Department of Biomedicine