TLR4 and neoplasm: During cellular stress, S100A8 and S100A9 is released as a heterodimer (e.g., calprotectin) into the extracellular space where it binds to TLR4 and initiate a signaling cascade that regulates inflammation, cell proliferation, differentiation, and tumor development in an NF-κB-dependent manner (Turovskaya et al., 2008).