s100a9 interaction with tlr4 promotes tumor growth与tlr4 s100a9互动促进肿瘤的生长.pdfVIP

S100A9 Interaction with TLR4 Promotes Tumor Growth ¨ 1 2 3 3 ¨ 3 ¨ 4 Eva Kallberg , Thomas Vogl , David Liberg , Anders Olsson , Per Bjork , Pernilla Wikstrom , 4 2 1 1 Anders Bergh , Johannes Roth , Fredrik Ivars , Tomas Leanderson * ¨ ¨ 1 Immunology Group, Lund University, Lund, Sweden, 2 Institute of Immunology, University of Munster, Munster, Germany, 3 Active Biotech AB, Lund, Sweden, ˚ ˚ 4 Department of Medical Bioscience, Umea University, Umea, Sweden Abstract By breeding TRAMP mice with S100A9 knock-out (S100A92/ 2) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A92/ 2 and TLR42/ 2, but not in RAGE 2/ 2 animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFb expression in splenic CD11b+ cells. Lastly, treatment o