Different Toll-Like Receptor Expression Patterns in Progression toward Cancer

Pattern recognition forms the basis ofthe innate immune system, allowing it tomaintain systemic homeostasis by reject-ing harmful molecular structures. Immunecells as well as epithelial cells located nearthe host–environment boundary, expresspattern-recognizing receptors, the activa-tion of which launches cascades lead-ing to immune response and apopto-sis (1,2). Human toll-like receptors(TLRs) 1–10, a family of trans-membranereceptor proteins comprising one typeof pattern-recognizing receptors, partic-ipate in these immunological processes.In healthy immune cells and epithelialcells, TLR 1, 2, 4, 5, 6, and 10 are usu-ally expressed on the cell surface, whereasTLR 3, 7, 8, and 9 are mainly expressedon the surfaces of endosomes, lysosomes,and endoplasmic reticulum (3). Microbialmolecular structures activating pattern-recognizing receptors are called pathogen-associated molecular patterns (PAMPs)(1,2). Besides exogenous structures, alsoendogenous molecules, released, for exam-ple, from inamed or damaged tissues, canactivate pattern-recognizing receptors andare called danger- or damage-associatedmolecular patterns (DAMPs) (4, 5). Lig-ands binding to TLR lead to the activa-tion of several intracellular signaling path-ways, activating, for instance, nuclear tran-scription factors that initiate host defensefunctions via secretion of co-stimulatoryfactors and cytokines (6). TLR activationleads also to regulation of gene expression,cell proliferation, differentiation, mitosis,cell-cycle regulation, and apoptosis (7).