lop oncogene-driven lymphoma to dissect the stroma conditions necessary for lymphoma progression. In the aggressive Em-Myc B cell lymphoma model we showed that the chemokine receptor CCR7 regulates access of lymphoma B cells to lymphoma-supporting niches within secondary lymphoid organs. Moreover, lodging within specific microanatomical sites launched a reciprocal cellular crosstalk with fibroblastic reticular stromal cells. This crosstalk was triggered by B cell-derived lymphotoxin, which acted upon the cognate lymphotoxin b-receptor on stromal cells. Subsequently, stromal cells provided the tumor cells with the survival factor Indian Hedgehog, but also with the chemoattractants CCL19 and CCL21 which allowed further recruitment of lymphoma B cells. Immuno-pharmacological interference with this crosstalk employing a lymphotoxin b-receptor immunoglobulin delayed lymphoma growth substantially (Rehm A. et al., Blood, 2011). In an indolent B cell lymphoma model, we currently extend these observations and aim at a more complete dissection of cellular stromal networks and signaling pathways that are crucial for lymphomagenesis in vivo. Selected Publications Fagerli, U-M, Ullrich, K, Stühmer, T, Holien, T, Köchert, K, Holt, RU, Bruland, O, Chatterjee, M, Nogai, H, Lenz, G, Shaughnessy, JD, Mathas, S, Sundan, A, Bargou, RC, Dörken, B, Børset, M, Janz, M. (2011). Serum/ glucocorticoid-regulated kinase 1 (SGK1) is a prominent target gene of the transcriptional response to cytokines in multiple myeloma and supports the growth of myeloma cells. Oncogene. 30, 3198-3206. Köchert, K, Ullrich, K, Kreher, S, Aster, JC, Kitagawa, M, Jöhrens, K, Anagnostopoulos, I, Jundt, F, Lamprecht, B, Zimber-Strobl, U, Stein, H, Janz, M, Dörken, B, Mathas, S. (2010). High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCHsignaling pathway in human lymphomas. Oncogene. 30, 1831-1840. Lamprecht*, B, Walter*, K, Kreher*, S, Kumar, R, Hummel, M, Lenze, D, Köchert, K, Bouhlel, MA, Richter, J, Soler, E, Stadhouders, R, Jöhrens, K, Wurster, KD, Callen, D, Harte, MF, Giefing, M, Barlow, R, Stein, H, Anagnostopoulos, I, Janz, M, Cockerill, P, Siebert, R, Dörken, B, Bonifer, C, Mathas, S. (2010). De-repression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nature Med. 16, 571-579. *) equal contribution. Rehm, A., Mensen, A., Schradi, K., Gerlach, K., Winter, S., Büchner, G., Dörken, B., Lipp, M., Höpken, U.E. (2011). Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs. Blood 118, 1020-1033 Wolf, J., Reimer, T.A., Schuck, S., Rüder, C., Gerlach, K., Müller, E.C., Otto, A., Dörken, B., Rehm, A. (2010). Role of EBAG9 protein in coat protein complex I-dependent glycoprotein maturation and secretion processes in tumor cells. FASEB J. 24, 4000-4019
Structure of the Group Group Leader Prof. Dr. Bernd Dörken Scientists Dr. Armin Rehm Dr. Stephan Mathas Dr. Martin Janz Dr. Stephan Kreher Dr. Björn Lamprecht
Ekaterina Perets*
Graduate students Jana Wolf* Angela Mensen* Stefanie Wittstock Marcel Gaetjen Karl Köchert* Shuang Li
Franziska Hummel
Katrin Ullrich Kathrin Wurster Technical Assistants Kerstin Gerlach Simone Lusatis Brigitte Wollert-Wulf Ute Nitschke Undergraduate Students Markus Biedermann * part of the period reported
Cancer Research 131