Mast cell chymase is present in uterine cervical carcinoma and it detaches viable and growing cervical squamous carcinoma cells from substratum in vitro

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 epith...

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Veröffentlicht in:Archives of Dermatological Research 2011-09, Vol.303 (7), p.499-512
Hauptverfasser: Diaconu, Nicolae-Costin, Rummukainen, Jaana, Naukkarinen, Anita, Mättö, Mikko, Harvima, Rauno J., Pelkonen, Jukka, Harvima, Ilkka T.
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container_end_page 512
container_issue 7
container_start_page 499
container_title Archives of Dermatological Research
container_volume 303
creator Diaconu, Nicolae-Costin
Rummukainen, Jaana
Naukkarinen, Anita
Mättö, Mikko
Harvima, Rauno J.
Pelkonen, Jukka
Harvima, Ilkka T.
description 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.
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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. 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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. 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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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21274549</pmid><doi>10.1007/s00403-011-1121-4</doi><tpages>14</tpages></addata></record>
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subjects Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Apoptosis - drug effects
Biological and medical sciences
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cell Adhesion - drug effects
Cell Growth Processes - drug effects
Cell Line, Tumor
Cell Survival - drug effects
Chymases - genetics
Chymases - metabolism
Dermatology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Female genital diseases
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Keratinocytes - drug effects
Keratinocytes - metabolism
Keratinocytes - pathology
Mast Cells - drug effects
Mast Cells - metabolism
Mast Cells - pathology
Medical sciences
Medicine
Medicine & Public Health
Neoplasm Metastasis
Original Paper
Serpins - genetics
Serpins - metabolism
Tumors
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
title Mast cell chymase is present in uterine cervical carcinoma and it detaches viable and growing cervical squamous carcinoma cells from substratum in vitro
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