Our group is interested in the communication of tumor cells with their microenvironment. It becomes more and more accepted that the tumor microenvironment is essential in the establishment of B-cell lymphomas. Understanding how different signaling pathways get activated through intrinsic signals of the tumor cell itself and extrinsic signals of the microenvironment, is one aim of our studies. Therefore, we investigate how the microenvironment is modulated by tumor cells and if interference with this modulation can be used as new therapeutic approaches for lymphoma patients. We could demonstrate that malignant B cells actively manipulate their microenvironment, creating a niche, which is essential for the survival of the tumor cells. The expression of protein kinase C-β (PKC-β) and the subsequent activation of NF-κB in the microenvironment play a decisive role in the pathogenesis of chronic lymphocytic leukemia (CLL). The detection of upregulated stromal PKC-β in biopsies from patients with acute lymphoblastic leukemia (ALL) and mantle cell lymphoma, not only in biopsies of CLL patients, suggests that this pathway may commonly be activated in a variety of hematological malignancies.
(1) Interference of the PKC-β/Nf-κB signaling pathway during interaction of tumor cells and their surrounding microenvironment in the remodeling process of the extracellular matrix
(2) Effect on other signaling pathways according to PKC-β expression in the tumor microenvironment
(3) Comparing the modulation of the microenvironment of different B cell malignancies
1. Lutzny G, Kocher T, Schmidt-Supprian M, Rudelius M, Klein-Hitpass L, Finch AJ, Dürig J, Wagner M, Haferlach C, Kohlmann A, Schnittger S, Seifert M, Wanninger S, Zaborsky N, Oostendorp R, Ruland J, Leitges M, Kuhnt T, Schäfer Y, Lampl B, Peschel C, Egle A, Rings-hausen I. Protein kinase C-β dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lympho-cytic leukemia B cells in vivo. Cancer Cell. 2013 Jan;23:77-92.
Comment in: Seton-Rogers S. Microenvironment: an accommodating host. Nat Rev Cancer. 2013 Mar; 13(3):145.
2. Huber S, Oelsner M, Decker T, zum Büschenfelde CM, Wagner M, Lutzny G, Kuhnt T, Schmidt B, Oostendorp RA, Peschel C, Ringshausen I. Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1. Leukemia. 2011 May;25(5):838-47.
3. zum Büschenfelde CM, Wagner M, Lutzny G, Oelsner M, Feuerstacke Y, Decker T, Bogner C, Peschel C, Ringshausen I. Recruitment of PKC-betaII to lipid rafts mediates apop-tosis- resistance in chronic lymphocytic leukemia expressing ZAP-70. Leukemia. 2010 Jan;24(1):141-52.
4. Bogner C, Dechow T, Ringshausen I, Wagner M, Oelsner M, Lutzny G, Licht T, Peschel C, Pastan I, Kreitman RJ, Decker T. Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl-2 expression. Br J Haematol. 2010 Jan;148(1):99-109.