The role of endothelial cells in the bone marrow microenvironmental induced modulation of gene-expression of multiple myeloma cells.

Multiple myeloma (MM) is an incurable plasma cell malignancy by the monoclonal expansion of plasma cells in the bone marrow (BM). Here the MM cells receive signals to survive and proliferate due to the existence of functional, mutual interactions between the MM cells and tge stromal BM cells. Moreover, the BM stroma is also involved in the clinical relevant drugresistance of the MM cells. The aim of the present project is to determine to what extent the EC and IGF-1 contribute to the BM microenvironmental induced modulation of gene-expression of multiple myeloma cells. By using Affymetrix cDNA microarrays (MOE430A) we will try to obtain an as wide as possible profile of the up- and downregulated genes in the MM cells after interaction with the BM endothelium and after treatment with IGF-1. We will mainly focus on genes involved in migration, adhesion, invasion, homing, proliferation, protection against cell death and radioresistence. Firstly we will use the experimental 5TMM murine model. Later on, we will confirm the obtained results with human samples.