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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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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 MCTC 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 MCTC 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. MCTC 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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Abbreviations

SCC:

Squamous cell carcinoma

MMP:

Metalloproteinase

ECM:

Extracellular matrix

MCTC :

Tryptase and chymase positive mast cell

MCT :

Tryptase positive mast cell

MCC :

Chymase positive mast cell

CIN:

Cervical intraepithelial neoplasia

IC:

Invasive carcinoma

SCCA:

Squamous cell carcinoma antigen

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Acknowledgments

The authors wish to thank Ms Anne Koivisto and Ms Katja Dufva for expert technical assistance and the Marie Curie Mobility Actions for Early Stage Researcher by the sixth framework of the EU commission (project no. 504926), the Finnish Cultural Foundation, Cancer Center of Eastern Finland and Kuopio University Hospital for financing this study.

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Authors and Affiliations

  1. Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland

    Nicolae-Costin Diaconu, Rauno J. Harvima & Ilkka T. Harvima

  2. Department of Pathology, Kuopio University Hospital, Kuopio, Finland

    Jaana Rummukainen & Anita Naukkarinen

  3. Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland

    Mikko Mättö & Jukka Pelkonen

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  1. Nicolae-Costin Diaconu
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  2. Jaana Rummukainen
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Correspondence to Nicolae-Costin Diaconu.

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Diaconu, NC., Rummukainen, J., Naukkarinen, A. et al. Mast cell chymase is present in uterine cervical carcinoma and it detaches viable and growing cervical squamous carcinoma cells from substratum in vitro. Arch Dermatol Res 303, 499–512 (2011). https://doi.org/10.1007/s00403-011-1121-4

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  • DOI: https://doi.org/10.1007/s00403-011-1121-4

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