Mechanisms of lymphatic metastasis of solid tumors with special focus on lysophospholipid- and chemokine receptors(in cooperation with P. M. Schlag, Charité)
Lymphatic metastasis at diagnosis is present in up to 25% of patients suffering from gastric cancer and is in the majority of cases responsible for the fatal outcome of the disease. The molecular mechanisms leading to metastasis appear to occur early in tumor development. We used laser capture microdissection to obtain highly purified cell populations from node-negative and node-positive primary gastric tumors as well as from the corresponding normal gastric mucosa and subsequently performed gene expression profiling to identify candidate genes implicated in the development of lymph node metastasis. Non-supervised clustering of expression profiles from tumor tissue revealed clearly distinguishable profiles from tumors with and without lymphatic metastasis. In contrast, expression profiles from normal gastric mucosa of patients with and without lymph node metastases could not be differentiated. By comparison of expression profiles from metastatic and non-metastatic primary tumors, we were able to define a significant number of genes at least 3 fold up- or downregulated in metastasized gastric cancer. The detailed biostatistical analysis is currently ongoing.