@article{Eleonora Fonte_Andreas Agathangelidis_Daniele Reverberi_Stavroula Ntoufa_Lydia Scarfò_Pamela Ranghetti_Giovanna Cutrona_Alessandra Tedeschi_Aliki Xochelli_Federico Caligaris-Cappio_Maurilio Ponzoni_Chrysoula Belessi_Zadie Davis_Miguel A. Piris_David Oscier_Paolo Ghia_Kostas Stamatopoulos_Marta Muzio_2015, place={Pavia, Italy}, title={Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation}, volume={100}, url={https://haematologica.org/article/view/7559}, DOI={10.3324/haematol.2014.119933}, abstractNote={Recent studies on splenic marginal zone lymphoma identified distinct mutations in genes belonging to the B-cell receptor and Toll-like receptor signaling pathways, thus pointing to their potential implication in the biology of the disease. However, limited data is available regarding the exact role of TLRs. We aimed at characterizing the expression pattern of TLRs in splenic marginal zone lymphoma cells and their functional impact on the activation, proliferation and viability of malignant cells <em>in vitro</em&gt;. Cells expressed significant levels of TLR1, TLR6, TLR7, TLR8, TLR9 and TLR10 mRNA; TLR2 and TLR4 showed a low, variable pattern of expression among patients whereas TLR3 and TLR5 mRNAs were undetectable; mRNA specific for TLR signaling molecules and adapters was also expressed. At the protein level, TLR1, TLR6, TLR7, TLR9 and TLR10 were detected. Stimulation of TLR1/2, TLR2/6 and TLR9 with their respective ligands triggered the activation of IRAK kinases, MAPK and NF-κB signaling pathways, and the induction of CD86 and CD25 activation molecules, although in a heterogeneous manner among different patient samples. TLR-induced activation and cell viability were also inhibited by a specific IRAK1/4 inhibitor, thus strongly supporting the specific role of TLR signaling in these processes. Furthermore, TLR2/6 and TLR9 stimulation also significantly increased cell proliferation. In conclusion, we demonstrate that splenic marginal zone lymphoma cells are equipped with functional TLR and signaling molecules and that the stimulation of TLR1/2, TLR2/6 and TLR9 may play a role in regulating disease pathobiology, likely promoting the expansion of the neoplastic clone.}, number={11}, journal={Haematologica}, author={Eleonora Fonte and Andreas Agathangelidis and Daniele Reverberi and Stavroula Ntoufa and Lydia Scarfò and Pamela Ranghetti and Giovanna Cutrona and Alessandra Tedeschi and Aliki Xochelli and Federico Caligaris-Cappio and Maurilio Ponzoni and Chrysoula Belessi and Zadie Davis and Miguel A. Piris and David Oscier and Paolo Ghia and Kostas Stamatopoulos and Marta Muzio}, year={2015}, month={Oct.}, pages={1460-1468} }