Altered expression of alpha 6 integrin subunit in oral squamous cell carcinoma and oral potentially malignant lesions.
The expression and distribution of integrin chains alpha 2, alpha 3, alpha 5, alpha 6, beta 1, beta 4, collagen type IV, laminin 1 and laminin 5 in oral squamous cell carcinoma (SCC) and oral keratoses with and without dysplasia (OL) have been studied by immunochemistry and western blotting. Focal interruptions of basement membrane protein staining were detected in SCC indicating a loss of continuity, whereas tumour nests were apparently completely surrounded by laminin 1, type IV collagen and laminin 5; the loss of basement membrane components in OL was found in only one specimen showing severe dysplasia. The localisation of integrins showed altered suprabasal and pericellular expression of the alpha 6 chain in all but one SCC, as well as in many OL samples, whereas the beta 4 subunit showed only a faint pericellular redistribution in SCC. In OL, beta 4 was often seen in a normal basally polarised distribution. Western blotting analysis confirmed that alpha 6 protein levels were abnormally high in cancerous lesions, whereas quantitative recovery of the beta 4 subunit in SCC was only minimal, suggesting a dissociation in the synthetic ratios of the two chains of the alpha 6 beta 4 heterodimer in SCC. Because alterations in the polarised expression of integrin alpha 6 beta 4 have been seen during epithelial tumour progression and wound healing, we suggest that the lack of restricted basal polarisation of alpha 6 could be an early but non-specific marker of oral malignancy, indicating that the generation of abnormal signals from the extracellular matrix may be involved.
Department of Oral Medicine and Periodontology, University of Torino, Italy.
P
P
Garzino-Demo
M
M
Carrozzo
L
L
Trusolino
P
P
Savoia
S
S
Gandolfo
P C
PC
Marchisio
D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D039503:Integrin alpha6; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D007972:Leukoplakia, Oral / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism
D015703:Antigens, CD; D039503:Integrin alpha6; D016023:Integrins; D007797:Laminin; D009363:Neoplasm Proteins; D003094:Collagen