<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma "^^ . "An aberrant expression of RAGE (receptor for advanced glycation end products)\r\nand its ligands, especially the S100-calgranulins has been demonstrated in squamous\r\ncell carcinoma of the upper aerodigestive tract. However, while S100-RAGE\r\nsignaling is commonly linked to the induction and maintenance of a cancer promoting\r\ninflammation, the question whether RAGE-signaling is causally linked with\r\nneoplastic transformation of keratinocytes in mucosal epithelia has not been addressed\r\nso far. The presence of S100-calgranulin positive infiltrating immune cells\r\nas well as S100-calgranulin expression in tumor cells was assessed in oropharyngeal\r\nsquamous cell carcinoma (OPSCC) on tissue microarrays (TMAs) containing tumor\r\nbiopsies from 188 human patients and compared with the amount of CD66b\r\npositive myeloid inflammatory cells on the same TMAs. To address the causal role\r\nof S100-RAGE signaling in the onset of oral carcinogenesis, the well established\r\nmouse model of 4-nitroquinoline-1-oxide (4-NQO) induced carcinogenesis was used\r\nto investigate tumor development in control and RAGE deficient (Rage-/-) mice as\r\nwell as mice deficient in S100a9 (S100a9-/-). While patient tumors varied strongly\r\nwith regard to the amount of S100-calgranulin and CD66b positive immune cells as\r\nwell as the expression pattern of S100-calgranulins in tumor cells, these features did\r\nnot correspond with clinico-pathological parameters or prognosis. In the onset of\r\noral and esophageal cancer, driven by 4-NQO induced genotoxic stress and in the\r\nabsence of an additional inflammatory stimulus, both Rage and S100a9 expression\r\nwas dispensable for tumor development. In both cohorts, mice developed tumors in\r\nthe esophagus and tongue with similar incidence rates and comparable multiplicity.\r\nAlso a detailed analysis of tumor sections by histological and immunohistochemical\r\nstaining revealed no difference in size or histological architecture of 4-NQO induced\r\nlesions, tumor cell proliferation and the number of inflammatory immune cells in\r\nthe tumor microenvironment. S100a8 and S100a9 were induced upon 4-NQO treatment\r\nindependent of the presence of RAGE, which may in part be explained by\r\ninduced transcript and protein levels of the Toll-like receptor 4 (Tlr4) in carcinogen\r\ntreated tissue, suggesting that signaling via the S100-TLR4 axis may compensate\r\nfor the lack of RAGE in early stages of tumor development. In summary, these data\r\npoint out that the impact of S100-RAGE signaling is critically depending on the\r\ncontext. While important in inflammation associated cancer, S100-RAGE signaling\r\nis dispensable in cancer caused by genotoxic stress without a promoting inflammation.\r\nWith regard to therapy and prevention, this illustrates the need of a clear\r\nstratification for the presence of a driving inflammation."^^ . "2013" . . . . . . . "Regina"^^ . "Mark"^^ . "Regina Mark"^^ . . . . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (PDF)"^^ . . . "Thesis_Regina-Mark.pdf"^^ . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (Other)"^^ . . . . . . "preview.jpg"^^ . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (Other)"^^ . . . . . . "medium.jpg"^^ . . . "S100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #14713 \n\nS100-RAGE signaling in the pathogenesis of Head and Neck Squamous Cell Carcinoma \n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .