AuthOr’s VIew

Our interest in the Ca2+-binding protein S100A9 was prompted by the observation that a family of small molecules in devel-opment for the treatment of autoimmune diseases and cancer, namely quinolone-3-carboxamides (Q compounds), bind to S100A9, thus inhibiting its interaction with innate immunity receptors such as Toll-like receptor 4 (TLR4) and recep-tor for advanced glycation end products (RAGE).1 Such initial findings were made in 2005, and since then several articles have been published that link S100A9 to tumor growth and metastasis.2,3 We decided to investigate whether the absence of S100A9, RAGE or TLR4 influ-ence tumor cell growth. We initially wanted to use a spontaneous tumor model in immu-nocompetent animals, since we suspected that part of the antitumor activity exerted by Q compounds4 would be mediated by the immune system. We had a special inter-est in prostate cancer as one Q compound is in clinical development for this specific indication.5 Hence, we started to breed S100A9−/ − and TLR4−/ − mice with TRAMP mice. The TRAMP model is a transgenic murine model of prostate cancer in which the SV40 large T antigen is expressed under the control of the probasin promoter.6 In our hands, TRAMP mice developed pal-pable tumors between weeks 20 and 30 of life, which was significantly delayed in both the S100A9−/ − and TLR4−/ − background.7 When we investigated S100A9 expression in prostate tumors, we noted that while S100A9 was barely absent in nonmalignant prostate tissue, it was readily detectable in S100A9 and tumor growth tomas Leanderson * and Fredrik Ivar