title: Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC.
abstract: Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC.
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN, USA.|Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Khammanivong
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Sorenson
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN, USA.|Mucosal and Vaccine Research Center, Minneapolis VA Medical Center, Minneapolis, MN, USA.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Ross
authors.affiliation: Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Erin B
authors.initials: EB
authors.lastname: Dickerson
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Rifat
authors.initials: R
authors.lastname: Hasina
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN, USA.|Mucosal and Vaccine Research Center, Minneapolis VA Medical Center, Minneapolis, MN, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D040501:Calgranulin A; D040502:Calgranulin B
keywords: S100A8/A9; calprotectin; carcinogenesis; cell cycle; differentiation