Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer.
Squamous cell carcinoma (SCC) of the oral cavity is a highly invasive tumour of stratified squamous epithelium that spreads through degradation of the basement membrane (BM) and extracellular matrix (ECM). There are currently no reliable tissue or serum markers to predict whether the tumour has metastasized at the time of diagnosis. Verrucous carcinoma (VC) of the oral cavity is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. Many matrix metalloproteinases (MMPs), such as MMP-1, -2, -7, -9, -13, and -14, as well as integrin receptors have been implicated in cancer invasion. Integrin alphavbeta6 is induced in SCC and appears to be involved in up-regulation of MMP-9 expression by oral keratinocytes and promotion of their migration. The aim of this study was to investigate whether the pattern of MMP expression or that of alphavbeta6 integrin contributes to the differences in the biological behaviour of oral SCC and VC. The results show that the less aggressive nature of oral VC may be connected to its MMP expression profile. Typically, VCs were devoid of epithelial MMP-3, -7, -9, -12 and -13 expression, compared with SCCs. MMP-19 was expressed by epithelial keratinocytes in hyperproliferative areas of verrucous hyperplasia, VC, and SCC, but was absent in the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative keratinocytes in VC as well as by invasive cancer cells in SCCs. MMP-10 was expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin expression was also detected in some cases of epithelial hyperplasia but was significantly more abundant in cancers at the invasive front. The absence of MMP-7, -9 and -12 from epithelial cells may serve as a good prognostic marker of non-invasive oral carcinoma. Blocking the activity of invasion-specific MMPs or alphavbeta6 integrin might offer novel therapeutic modalities in early-stage oral carcinoma.
Impola
U
U
Department of Dermatology, University of Helsinki, Helsinki, Finland.
Uitto
V J
VJ
Hietanen
J
J
Hakkinen
L
L
Zhang
L
L
Larjava
H
H
Isaka
K
K
Saarialho-Kere
U
U
D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018289:Carcinoma, Verrucous / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D017364:Collagenases / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D006965:Hyperplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D016023:Integrins / Q000032:analysis; D053506:Matrix Metalloproteinase 10; D053508:Matrix Metalloproteinase 12; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020783:Matrix Metalloproteinase 7 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D020782:Matrix Metalloproteinases / Q000032:analysis; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000032:analysis*; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D000097794:Kalinin
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D017364:Collagenases; D016023:Integrins; D053506:Matrix Metalloproteinase 10; D053508:Matrix Metalloproteinase 12; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; D000097794:Kalinin; C073878:integrin alphavbeta6; C507079:MMP13 protein, human; C410599:MMP26 protein, human; C108362:matrix metalloproteinase 19; C507122:MMP12 protein, human