In multiple myeloma (MM), interactions of bone marrow stromal cells with the malignant plasma cells have gained significant

importance as targets for novel therapeutic agents. Based upon these observations, we aimed at analyzing in detail the secretory capacity of bone marrow fibroblasts obtained from patients with MM in order to better Selleck AR-13324 understand their contribution to disease progression. We therefore analyzed the secretome of primary bone marrow fibroblasts of MM patients by proteome profiling based on highly sensitive mass spectrometry. Normal skin and bone marrow fibroblasts were found to secrete various extracellular matrix (ECM) proteins including fibronectin, collagens and laminins, in addition to some chemokines and cytokines including CXCL12, follistatin-like 1, insulin-like growth factor binding proteins 4, 5 and 7; and SPARC. In contrast, bone-marrow-derived fibroblasts from MM patients secreted increased amounts of ECM

proteins and alpha-fetoprotein in addition to insulin-like growth factor II, stem cell growth factor and matrix metalloproteinase-2. Co-culture of primary MM cells with these fibroblasts further stimulated the secretion of ECM proteins, of cytokines such as inhibin beta A chain and growth factors such as connective BMS202 datasheet tissue growth factor, which might be relevant to support the malignant clone. Analyses of the secretion capacity of PIK3C2G bone marrow fibroblasts from patients with MGUS show that their secretome profile is also different compared to that of normal bone marrow fibroblasts. Proteome Vadimezan concentration profiling of secreted proteins may thus help to identify relevant tumor-associated proteins, to increase our understanding

of cell cooperativity and thereby increase our understanding of progression events in monoclonal gammopathies. O133 How do Endothelial Cells Shape the Tissue Microenvironment? A Proteomic Approach Thomas Mohr 1 , Stefan Stättner2, Nina Gundacker1, Verena Haudek1, Astrid Slany1, Christine Brostjan3, Reinhard Horvat4, Josef Karner2, Michael Micksche1, Christopher Gerner1 1 Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria, 2 Department of Surgery, Social Medical Center South, Vienna, Austria, 3 Department of Surgery Research Laboratories, Medical University of Vienna, Vienna, Austria, 4 Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria Endothelial cells (EC) substantially shape the tissue microenvironment which plays a critical role in tumor progression. We established protein maps of the secretome of human umbilical vein endothelial cells (HUVEC), human liver endothelial cells (HLEC) and human tumor derived endothelial cells (HTEC) from ovarian carcinoma. HLEC and HTEC were isolated using magnetic beads (anti CD31).