Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma |
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Authors: | Sari?Suomela Virve?Koljonen Tiina?Skoog Heli?Kukko Tom?B?hling Ulpu?Saarialho-Kere |
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Institution: | 1.Department of Dermatology,University of Helsinki,Helsinki,Finland;2.Department of Pathology,University of Helsinki and Helsinki University Central Hospital,Helsinki,Finland;3.Department of Plastic Surgery,Helsinki University Central Hospital,Helsinki,Finland;4.Department of Clinical Science and Education and Section of Dermatology,Karolinska Institutet at Stockholm S?der Hospital,Stockholm,Sweden;5.Department of Biosciences and Nutrition,Karolinska Institutet at Novum,Huddinge,Sweden;6.HUSLAB,Helsinki University Central Hospital,Helsinki,Finland;7.Department of Dermatology,Helsinki University Central Hospital,Helsinki,Finland |
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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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