Alpha v beta 6 integrin down-regulates the MMP-13 expression in oral squamous cell carcinoma cells.
The integrin alphavbeta6, a receptor for fibronectin, vitronectin, tenascin and TGF-beta latency-associated peptide (LAP), is not detectable on normal oral epithelium but is neo-expressed in oral squamous cell carcinomas (OSCC) and epithelial dysplasia. Previously it has been shown that alphavbeta6 integrin can up-regulate MMP-3 and -9 expression in OSCC cells. Using beta6-transfected and control OSCC cells we demonstrate that alphavbeta6 integrin down-regulates MMP-13 expression at both mRNA and protein level. Although expressing less MMP-13, beta6-transfected cells were found to have similar collagenolytic activity as control cells and invade at similar levels through type I collagen. Growth of the tumour cells in organotypic culture and confocal microscopy confirmed low levels of MMP-13 in cells with high alphavbeta6 expression. Furthermore, human squamous cell carcinomas of the tongue with high expression of alphavbeta6 showed lower MMP-13 levels than carcinomas with low levels of alphavbeta6. Our results suggest that alphavbeta6 down-regulates MMP-13 expression in OSCC cells and that MMP-13 is not essential for the degradation of type I collagen by OSCC cells.
Ylipalosaari
M
M
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, PO Box 5281, FIN-90014 Oulu, Finland.
Thomas
G J
GJ
Nystrom
M
M
Salhimi
S
S
Marshall
J F
JF
Huotari
V
V
Tervahartiala
T
T
Sorsa
T
T
Salo
T
T
D000951:Antigens, Neoplasm / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D053509:Matrix Metalloproteinase 13; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism
D000951:Antigens, Neoplasm; D024042:Collagen Type I; D016023:Integrins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D012333:RNA, Messenger; C073878:integrin alphavbeta6; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1