title: Mast cell chymase is present in uterine cervical carcinoma and it detaches viable and growing cervical squamous carcinoma cells from substratum in vitro.
abstract: Increased numbers of mast cells is a typical feature of a variety of human cancers. The major mediators in the secretory granules of the MC(TC) type of mast cells, serine proteinases tryptase and chymase, may be involved in squamous cell carcinoma (SCC) lesions by inducing matrix remodeling and epithelial cell detachment. The objective of this study was to analyze immunohistochemically whether MC(TC) mast cells as well as protease inhibitors, squamous cell carcinoma antigens (SCCAs), are present in the uterine cervical SCC. In addition, the effect of tryptase and chymase on uterine cervical SCC cell lines was studied in vitro. Here we report that tryptase- and chymase-positive mast cells are present in significant numbers in the peritumoral stroma of SCC lesions. Also, weak SCCA-2 immunoreactivity is observed in the SCC lesions, but only SCCA-1 in uterine cervical specimens with nonspecific inflammation. In cell cultures, especially chymase, but not tryptase, was shown to induce effective detachment of viable, growing and non-apoptotic SiHa SCC cells from substratum. Chymase also detached viable ME-180 SCC cells from substratum as well as degraded fibronectin. In contrast, normal keratinocytes underwent apoptotic cell death after similar prolonged chymase treatment. No inhibition of chymase was detected by SiHa cell sonicates nor did these cells express marked SCCA immunopositivity. MC(TC) mast cells containing tryptase and chymase are present in the peritumoral stroma of uterine cervical SCC and the malignant cells are only weakly immunoreactive for the chymase inhibitor SCCA-2. It is chymase that appears to be capable of inducing effective detachment of viable and growing SCC cells and therefore, it may release SCC cells from a tumor leading to spreading of malignant cells.
authors.affiliation: Department of Dermatology, University of Eastern Finland and Kuopio University Hospital. nicolae-costin.diaconu@kuh.fi
authors.forename: Nicolae-Costin
authors.initials: NC
authors.lastname: Diaconu
authors.forename: Jaana
authors.initials: J
authors.lastname: Rummukainen
authors.forename: Anita
authors.initials: A
authors.lastname: Naukkarinen
authors.forename: Mikko
authors.initials: M
authors.lastname: Mättö
authors.forename: Rauno J
authors.initials: RJ
authors.lastname: Harvima
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
authors.forename: Ilkka T
authors.initials: IT
authors.lastname: Harvima
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053818:Chymases / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D053818:Chymases