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Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma

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Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with poor outcome and increasing incidence. We examined by immunohistochemistry the expression of three novel matrix metalloproteinases (MMPs)—MMP-21, MMP-26, and MMP-28—in 44 primary MCC tumors and six lymph node metastases while MMP-10 served as a positive control. Their mRNA expression was also studied in the UISO MCC cell line basally and after various stimulations using quantitative real-time PCR. MMP-28 was observed in tumor cells of 15/44 samples especially in tumors <2 cm in diameter (p = 0.015) while 21/44 specimens showed MMP-28 in the tumor stroma. Expression of MMP-21 was demonstrated in tumor cells of 13/43 samples. MMP-26, instead, was positive in stromal cells (17/44) and its expression associated with tumors ≥2 cm in diameter (p = 0.006). Stromal expression of MMP-10 was the most frequent finding of the studied samples (31/44), but MMP-10 was detected also in tumor cells (17/44). Most of the metastatic lymph nodes expressed MMP-10 and MMP-26. MMP-10, MMP-21, and MMP-28 mRNAs were basally expressed by the UISO cells, and the corresponding proteins were detectable by immunostaining of cultured cells. IFN-α and TNF-α downregulated MMP-21 and MMP-28 expression. Our results suggest that novel MMPs may have a role in MCC pathogenesis: especially that MMP-26 expression in stroma is associated with larger tumors with poor prognosis. Expression of MMP-21 and MMP-28 seems to associate with the tumors of lesser malignant potential. We also confirm the previous finding on the role of MMP-10 in MCC pathogenesis.

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Acknowledgments

We thank Prof. Das Gupta and Dr. Roland Houben for UISO cells, Prof. Jorma Keski-Oja for MMP-28-overexpressing A549 cells, Ph. D. Jenita Pärssinen for contributions in the early phases of this study, and Ms. Alli Tallqvist and Ms. Jonna Jantunen for skillful technical assistance. This study was supported by the Academy of Finland, Finnish Cancer Foundation, Finska Läkaresällskapet, Helsinki University Central Hospital Research Fund (TYH2009233), Finland and Cancerfonden, the Swedish Research Council, and Edvard Welander–Finsen Foundation (TS), Sweden. Prof. Saarialho-Kere passed away during the processing of the manuscript. This article is dedicated to her memory.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Dermatology, University of Helsinki, Meilahdentie 2, 00250, Helsinki, Finland

    Sari Suomela & Ulpu Saarialho-Kere

  2. Department of Pathology, University of Helsinki and Helsinki University Central Hospital, PO 400, 00290 HUS, Helsinki, Finland

    Tom Böhling

  3. Department of Plastic Surgery, Helsinki University Central Hospital, PO 266, 00290 HUS, Helsinki, Finland

    Virve Koljonen & Heli Kukko

  4. Department of Clinical Science and Education and Section of Dermatology, Karolinska Institutet at Stockholm Söder Hospital, Stockholm, Sweden

    Tiina Skoog & Ulpu Saarialho-Kere

  5. Department of Biosciences and Nutrition, Karolinska Institutet at Novum, 14157, Huddinge, Sweden

    Tiina Skoog

  6. HUSLAB, Helsinki University Central Hospital, PO 720, 00290 HUS, Helsinki, Finland

    Tom Böhling

  7. Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, 00250, Helsinki, Finland

    Sari Suomela

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  1. Sari Suomela
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Correspondence to Sari Suomela.

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Suomela, S., Koljonen, V., Skoog, T. et al. Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma. Virchows Arch 455, 495–503 (2009). https://doi.org/10.1007/s00428-009-0856-1

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  • DOI: https://doi.org/10.1007/s00428-009-0856-1

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