Calprotectin and the Initiation and Progression of Head and Neck Cancer.

摘要: Calprotectin (S100A8/A9), a heterodimeric complex of calcium-binding proteins S100A8 and S100A9, is encoded by genes mapping to the chromosomal locus 1q21.3 epidermal differentiation complex. Whereas extracellular calprotectin shows proinflammatory antimicrobial properties signaling through RAGE TLR4, intracytoplasmic S100A8/A9 appears be important for cellular development, maintenance, survival. constitutively expressed in myeloid cells stratified mucosal epithelia lining oropharyngeal genitourinary mucosae. While upregulated adenocarcinomas other cancers, mRNA protein levels decline head neck squamous cell carcinoma (HNSCC). also lost during preneoplasia (dysplasia). decrease does not correlate with clinical stage (TNM) HNSCC. When cells, downregulates matrix metalloproteinase 2 expression inhibits invasion migration vitro. regulates cycle progression decelerates cancer proliferation arresting at G2/M checkpoint phosphatase 2α-dependent manner. In HNSCC, S100A9 coregulate gene networks controlling development differentiation, cell-to-cell signaling, morphology, while downregulate invasion- tumorigenesis-associated genes. Indeed, tumor formation capacity attenuated S100A8/A9-expressing vivo. Hence, intracellular function as suppressor carcinogenesis. compared S100A8/A9-low HNSCC based on analysis TCGA, S100A8/A9-high significant upregulation apoptosis-related genes, including multiple caspases. Accordingly, facilitates DNA damage responses promotes apoptotic death, confers sensitivity cisplatin X-radiation milieu, loss strongly associates poor higher grading, EGFR upregulation, increased methylation, and, finally, poorer overall survival patients multifaceted protective role against