Multiple myeloma-endothelium: 2D and 3D systems to study notch signaling

INTRODUCTION: Multiple myeloma (MM) is an incurable disease that depens on interactions with bone marrow (BM) microenvironment. Angiogenesis is a key mechanism, which supports MM survival [1]. In MM, Notch pathway displays ligands deregulation. It is involved in MM-microenvironment crosstalk but its role in MM-endothelial cells (ECs) crosstalk is not clear. The aim of the project is to study Notch involvement in MM-ECs interaction to provide rational for anti-Notch therapy. EXPERIMENTAL MODEL: I used a MM cell line silenced for Notch ligands, Jagged1-2. Using 2D co-culture system of MM-EC cells, I assessed relevant angiogenic features. Moreover, I exploited the physiologic features of decellularized extracellular matrix (dECM) to obtain 3D system to mimic bone niche. RESULTS: Matrigel assay of ECs with silenced MM cells showed an impact on ECs distribution and vessels formation. A home-made dECM was successfully obtained and supported cell seeding and organoid generation. Apoptosis analysis of organoids composed by BM stroma and MM revealed that BM stroma supports MM survival by reducing number of MM apoptotic cells compared to single culture of MM. CONCLUSION: These preliminary results indicate a novel role for Notch signaling in MM-EC crosstalk. 3D organoid can be seen as tool to investigate microenvironment organization and to screen novel drugs. REFERENCES: [1] Ribatti, D., Moschetta, M. & Vacca, A., Microenvironment and multiple myeloma spread. Thrombosis Research, 2014;