alpha v beta 6 Integrin upregulates matrix metalloproteinase 9 and promotes migration of normal oral keratinocytes.
The integrin alpha v beta 6 is a fibronectin receptor that is undetectable on normal keratinocytes in situ, but is increased significantly in wound healing and in culture-established keratinocytes, suggesting that it may promote changes associated with cell motility. Using normal human oral keratinocytes we have shown that cultured cells express relatively high levels of alpha v beta 6 and this integrin has a functional role in both cell adhesion and migration towards fibronectin. We provide experimental evidence that the increased expression of alpha v beta 6 by normal human oral keratinocytes results in coordinate changes, which promote a more migratory phenotype. Thus increased expression of alpha v beta 6 results in a fibronectin-dependent increase in pro-matrix metalloproteinase 9, matrix metalloproteinase 9 activity increases normal human oral keratinocyte migration, and this may be further dependent on plasmin activation. The results suggest a key role for alpha v beta 6 in these processes and indicate a coordinated link between alpha v beta 6 expression and upregulation of matrix metalloproteinase 9. It appears that alpha v beta 6 may function in normal human oral keratinocyte migration through matrix-metalloproteinase-9-dependent and -independent mechanisms.
Thomas
G J
GJ
Department of Oral Pathology, Eastman Dental Institute, University College London, UK.
Poomsawat
S
S
Lewis
M P
MP
Hart
I R
IR
Speight
P M
PM
Marshall
J F
JF
D000951:Antigens, Neoplasm; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D015603:Keratinocytes / Q000201:enzymology / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009061:Mouth Mucosa / Q000166:cytology; D019030:Receptors, Vitronectin; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D005353:Fibronectins; D016023:Integrins; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C073878:integrin alphavbeta6; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9