Matrix metalloproteinases 21 and 26 are differentially expressed in esophageal squamous cell cancer.
Matrix metalloproteinase 21 (MMP-21) and MMP-26 (matrilysin-2) are the two newest members of the human MMP gene family that have both been suggested to play an important role in epithelial tumor progression and to be regulated via the Wnt signaling pathway. We studied their expression in 34 esophageal squamous cell carcinomas and non-neoplastic epithelium. MMP-21 protein was detected in cancer cells and inflammatory cells at the invasive front. Its expression was associated with invasion, inflammation, apoptotic and well-differentiated areas of the tumors, but not with cell proliferation. Unlike MMP-21, MMP-26 protein was already upregulated in incipient invasion and its expression associated with regions of low differentiation being more sporadic at the invasive front. MMP-21 was detected basally in KYSE-30 and OE21 esophageal squamous cell carcinoma cells, while MMP-26 was absent. None of the several cytokines and matrices tested were capable of consistently upregulating MMP-21 or MMP-26 mRNA expression in these two cell lines. Our results suggest that during esophageal tumorigenesis, MMP-21 and MMP-26 have different, unique expression patterns both being tightly regulated and induced in the vicinity of inflammation. MMP-21 may provide a marker for differentiating tumor areas. The putative role of MMP-26 as a marker of dysplasia and incipient invasion warrants further studies.
Ahokas
Katja
K
Department of Dermatology, Helsinki University Central Hospital, and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Karjalainen-Lindsberg
Marja-Liisa
ML
Sihvo
Eero
E
Isaka
Keiichi
K
Salo
Jarmo
J
Saarialho-Kere
Ulpu
U
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology
D014408:Biomarkers, Tumor; C471969:MMP21 protein, human; C410599:MMP26 protein, human; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted