title: Cell Surface Human Airway Trypsin-Like Protease Is Lost During Squamous Cell Carcinogenesis.
abstract: Cancer progression is accompanied by increased levels of extracellular proteases that are capable of remodeling the extracellular matrix, as well as cleaving and activating growth factors and receptors that are involved in pro-cancerous signaling pathways. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression, however, the expression or function of the TTSP Human Airway Trypsin-like protease (HAT) in carcinogenesis has not been examined. In the present study we aimed to determine the expression of HAT during squamous cell carcinogenesis. HAT transcript is present in several tissues containing stratified squamous epithelium and decreased expression is observed in carcinomas. We determined that HAT protein is consistently expressed on the cell surface in suprabasal/apical layers of squamous cells in healthy cervical and esophageal epithelia. To assess whether HAT protein is differentially expressed in normal tissue versus tissue in different stages of carcinogenesis, we performed a comprehensive immunohistochemical analysis of HAT protein expression levels and localization in arrays of paraffin embedded human cervical and esophageal carcinomas compared to the corresponding normal tissue. We found that HAT protein is expressed in the non-proliferating, differentiated cellular strata and is lost during the dedifferentiation of epithelial cells, a hallmark of squamous cell carcinogenesis. Thus, HAT expression may potentially be useful as a marker for clinical grading and assessment of patient prognosis in squamous cell carcinomas.
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Michael J
authors: MJ
authors: Duhaime
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Khaliph O
authors: KO
authors: Page
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Fausto A
authors: FA
authors: Varela
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Cancer Biology Graduate Program, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Andrew S
authors: AS
authors: Murray
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Michael E
authors: ME
authors: Silverman
authors: Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Gina L
authors: GL
authors: Zoratti
authors: Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors: Karin
authors: K
authors: List
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D012697:Serine Endopeptidases; C112256:human airway trypsin-like protease