Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma.
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 >or=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-alpha and TNF-alpha 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.
Suomela
Sari
S
Department of Dermatology, University of Helsinki, Meilahdentie 2, 00250, Helsinki, Finland. sari.suomela@helsinki.fi
Koljonen
Virve
V
Skoog
Tiina
T
Kukko
Heli
H
Böhling
Tom
T
Saarialho-Kere
Ulpu
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
C471969:MMP21 protein, human; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D053506:Matrix Metalloproteinase 10