AlphaVbeta6 integrin promotes invasion of squamous carcinoma cells through up-regulation of matrix metalloproteinase-9.
The integrin alphaVbeta6 is a fibronectin receptor, which is not detectable on normal epithelium but is neo-expressed in oral epithelial dysplasia and oral squamous-cell carcinoma (SCC), suggesting a role in promoting malignant behaviour and tumour progression. We used transfection and retroviral infection to create a panel of SCC cell lines expressing various levels of alphaVbeta6 to examine this possibility. We found that increased expression of alphaVbeta6 in malignant keratinocytes up-regulates MMP-9 and MMP-2 expression and promotes invasion in an MMP-9-dependent manner. Our results suggest a possible mechanism for the involvement of alphaVbeta6 in squamous carcinoma in vivo.
Thomas
G J
GJ
Department of Oral Pathology, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8L6, United Kingdom.
Lewis
M P
MP
Hart
I R
IR
Marshall
J F
JF
Speight
P M
PM
D000818:Animals; D000951:Antigens, Neoplasm; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement; D004789:Enzyme Activation; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D014162:Transfection
D000951:Antigens, Neoplasm; D016023:Integrins; C073878:integrin alphavbeta6; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9