Project Details
Projekt
Determining the supporting mesenchymal cell lineages and their interactions with multiple myeloma
Applicant
Dr. Matthias Kieslinger
Subject Area
Hematology, Oncology
Term
from 2011 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 179902948
The microenvironment for hematologic malignancies like multiple myeloma consists of mesenchymal cells of the bone marrow, which presumably play a central role in their support. We could show that the transcription factor Ebf2 is expressed in mesenchymal cells and is necessary for the support of normal immature hematopoietic cells. Likewise, Ebf2 expressing cells also support malignant cells, including leukemia and myeloma cells, and the deletion of Ebf2 affects this supportive capacity to some degree. Since the highly homologous Ebf1 and Ebf3 genes are also expressed in mesenchymal cells, redundancy may obscure the true contribution of Ebf proteins. We have established an RNAi-based approach that allows the down-regulation of all three Ebf family members concomitantly. Co-culture experiments show that this affects the support of malignant cells beyond the deletion of Ebf2 alone. Therefore, our working hypothesis is that Ebf proteins define a niche for malignant hematopoietic cells and are functionally required for this supportive role. We will use the RNAi technique to establish a mouse model that allows manipulation of the tumor-supportive capacity of mesenchymal cells in vivo. This will help to define the role of osteoblastic and mesenchymal cells in the support of malignancies like multiple myeloma and to identify proteins involved in cell-cell communication between multiple myeloma and supporting cells.
DFG Programme
Research Units
