Study of molecular interactions between endothelial cells and multiple myeloma cells and their role in the regulation of tumor growth and migration.

The presence of myeloma cells in circulation and their extravasation towards bone marrow, implicates that these cells must have the potential to bind to endothelial cells and to migrate through the endothelium. The recent observation that bone marrow of myeloma patients shows an increased microvessel density suggests that also de novo blood vessel formation or angiogenesis plays an essential role in the pathenogenesis of this malignant disease. This project aims to examine molecular interactions that are involved. In the first part we will focus on the identification of mechanisms, involved in the extravasation of myeloma cells. Special attention will be given to the specific role of adhesion molecules and metalloproteinases in this process. In the second part we will concentrate on mechanisms involved in angiogenesis in MM. Both parts will be performed by in vitro experiments using a panel of human myeloma cell lines (with medullary orgin) and the 5T mouse model. In the last part we will investigate the in vivo effect of specific MMP- and/or angiogenesis-inhibitors. Therefore, the 5T2 MM mouse myeloma model will be used.