Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas.
BACKGROUND
Patients with recessive dystrophic epidermolysis bullosa (RDEB) have an increased risk of developing rapidly progressive and metastatic cutaneous squamous cell carcinomas (SCC). It is unclear why these SCC behave more aggressively than sporadic SCC. Matrix metalloproteinases (MMP) are a family of endopeptidases that contribute to growth, invasion and metastasis of SCC. The role of MMP in RDEB-associated SCC is not known.


OBJECTIVE
To investigate the expression of MMP-7, MMP-13 and MMP-9 in RDEB-associated SCC in comparison with sporadic SCC and Bowen's disease.


METHODS
Immunohistochemical analysis of 25 RDEB-associated SCC, 61 sporadic SCC and 28 sporadic lesions of Bowen's disease was carried out using monoclonal antibodies for MMP-7, MMP-9, MMP-13 and E-cadherin and syndecan-1.


RESULTS
MMP-7 was detected in all RDEB-associated SCC, in tumour cells within the invasive edge, where E-cadherin and syndecan-1 were markedly diminished or absent. MMP-7 expression was also observed in 98% of sporadic SCC and in 68% of Bowen's diseases. MMP-7 staining was significantly stronger in RDEB-associated SCC than in sporadic SCC, and was most abundant in poorly differentiated tumours. MMP-13 was detected in tumour cells in 96% of RDEB-associated SCC and in all sporadic cutaneous SCC. MMP-9 was detected in the inflammatory cells in all SCC examined.


CONCLUSIONS
These results identify MMP-7 and MMP-13 as tumour cell-specific markers for SCC progression and as potential therapeutic targets in RDEB-associated SCC. The pattern of immunolabelling suggests that MMP-7 may shed E-cadherin and syndecan-1 from the SCC cell surface.
Kivisaari
A K
AK
Department of Dermatology, University of Turku and Turku University Central Hospital, Turku, Finland.
Kallajoki
M
M
Mirtti
T
T
McGrath
J A
JA
Bauer
J W
JW
Weber
F
F
Königová
R
R
Sawamura
D
D
Sato-Matsumura
K C
KC
Shimizu
H
H
Csikós
M
M
Sinemus
K
K
Beckert
W
W
Kähäri
V-M
VM
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D045744:Cell Line, Tumor; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism* / Q000627:therapeutic use; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism* / Q000627:therapeutic use; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism*
D014408:Biomarkers, Tumor; D053509:Matrix Metalloproteinase 13; D020783:Matrix Metalloproteinase 7