Characterization of the Notch/PKCβ/NF-κB signalling pathway in the tumor microenvironment of chronic lymphocytic leukemia

点击翻译按钮获取中文摘要

The tumor microenvironment (TME) is an essential component of tumor propagation and progression. The circular contact with the bone marrow and the lymphoid tissues is one of the hallmarks of chronic lymphocytic leukemia (CLL). Importantly, the metabolism of cancer cells differs largely to that of normal cells. Our data demonstrate PKCβ-dependent changes in the glucose metabolism of bone marrow stromal cells (BMSCs) after CLL contact. In this proposal we want to further analyse the effect of insulin to the metabolism of BMSCs proficient and deficient for PKCβ in response to CLL contact. Additionally, we describe a role of the stromal Notch signaling that is required for the activation of Wnt signaling in CLL cells. Moreover, our data indicate a connection of Notch and the PKCβ/NF-κB signaling in BMSCs. This correlation will be investigated in this proposal using our 3D BMSC/leukemia model. Based on the complex links between Notch, PKCβ, NF-κB and the autophagy/ EMT regulation, analysis of the crosstalk between autophagy and EMT in the bone marrow niche of CLL in a 3D leukemia/stroma model will be addressed in this proposal.