Oral Diseases (1999) 5, 210–217  1999 Stockton Press All rights reserved. 1354-523X/99 $12.00 http://www.stockton-press.co.uk/od Expression of integrin 9 subunit and tenascin in oral leukoplakia, lichen planus, and squamous cell carcinoma L Ha ¨kkinen 1 , T Kainulainen 2 , T Salo 2 , R Grenman 3 , H Larjava 1 1 University of British Columbia, Faculty of Dentistry, Department of Oral Biological and Medical Sciences, Vancouver, B.C., Canada; 2 Department of Diagnostics and Oral Medicine, University of Oulu, and University Central Hospital, Oulu, Finland; 3 Department of Otorhinolaryngology, Head and Neck Surgery, University of Turku, Finland OBJECTIVES: Integrin 9 subunit is a member of 1 integrin family and binds tenascin (TN). It is expressed by stratified squamous epithelium and may be associated with cell differentiation and growth. W e studied if the expression of 9 integrin and TN is altered in leuko- plakia, lichen planus, and squamous cell carcinoma (SCC). METHODS: Frozen sections of tissue samples obtained from normal human keratinized (16 subjects) and non- keratinized (three subjects) oral mucosa, oral leukopak- ias with dysplasia (19 subjects), reticular type lichen planus (nine subjects), or oral mucosal SCC (23 subjects) were stained immunohistochemically with antibodies against 9 integrin and TN. RESULTS: In contrast to its most prominent localization at the cell membranes of the basal epithelial cells in the normal mucosa, 9 integrin was localized in a more dif- fuse pattern with focal loss of expression at the epithelial cell membranes in leukoplakic dysplasia, lichen planus, and SCC. In some areas of SCC, 9 integrin localized throughout all cell layers of the tumor epithelium. In most areas, 9 integrin colocalized with TN but in heav- ily inflamed areas there was focal loss of TN and 9 inte- grin at the basement membrane zone. CONCLUSIONS: The findings show that 9 integrin expression is altered in leukoplakic dysplasia, lichen planus, and SCC. Keywords: 9 integrin; tenascin; leukoplakia; lichen planus; squamous cell carcinoma Introduction Cell functions are regulated by interactions between cells and extracellular matrix molecules. Tenascin (TN), a large extracellular matrix glycoprotein, is normally expressed during development and wound healing and regulates cell Correspondence: Dr Lari Ha ¨kkinen, University of British Columbia, Fac- ulty of Dentistry, Department of Oral Biological and Medical Sciences, 2199 Wesbrook Mall, Vancouver, B.C., Canada V6T 1Z3. Tel: 001 604 822 0744, Fax: 001 604 822 3562, E-mail: lari.hakkinenutu.fi Received 28 October 1998; revised 8 December 1998; accepted 13 Janu- ary 1999 migration and growth (Chiquet-Ehrismann et al, 1995; Crossin, 1996). In oral squamous cell carcinoma, epithelial dysplasia, leukoplakia, and hyperplasia (Tiitta et al, 1994; Becker and Schuppan, 1995; Ramirez-Amador et al, 1996; Mighell et al, 1997), expression of TN is upregulated in the connective tissue under the epithelium. Expression of integrin-type extracellular matrix receptors by epithelial cells is also altered in these processes (Jones et al, 1993; Shrestha et al, 1994; Becker and Schuppan, 1995; Kosmehl et al, 1995; Ramirez-Amador et al, 1996; Jones et al, 1997). Integrins are a family of integral cell surface recep- tors composed of noncovalently associated  and  sub- units and mediate information between cells and the extra- cellular matrix. To date, 16 and 8 subunits are known that can combine to form at least 22 different  hetero- dimers. Ligand binding by integrins can regulate several key cellular functions including growth, adhesion, migration, and gene expression (reviewed by Brakebusch et al, 1997; Katz and Yamada, 1997). Cell adhesion to TN is mediated by several integrins in a cell-type specific manner. Depending on cell type, TN can serve as a ligand for up to five integrins of which v3, v6, 91, and 81 integrins recognize the third fib- ronectin type III repeat in TN (Prieto et al, 1992; Srirama- rao et al, 1993; Yokosaki et al, 1994; Schnapp et al, 1995). The migration of endothelial cells on TN is, however, mediated by 21 integrin that recognizes the terminal fibrinogen like domain in vitro (Sriramarao et al, 1993). Integrin 9 subunit is a recently characterized member of the 1 integrin family (Palmer et al, 1993) that is expressed mostly by stratified squamous epithelium in skin, cornea, trachea, larynx, and esophagus (Stepp et al, 1995; Wang et al, 1995; Stepp and Zhu, 1997). It recognizes, in addition to TN (Yokosaki et al, 1994), a cryptic sequence in osteo- pontin exposed by cleavage by thrombin (Smith et al, 1996; Smith and Giachelli, 1998). The expression of 9 integrin coincides with the stratification of the epithelium during development (Wang et al, 1995). In addition, 9 integrin expression is abundant in the area of stem cells of the cornea (Stepp et al, 1995; Stepp and Zhu, 1997) and in the basal cells of the skin epithelium and hair germs (Wang et al, 1995) suggesting that 9 integrin expression may be associated with cell proliferation. Accordingly, interaction between 9 integrin and TN can directly stimulate cell pro- liferation in cell culture (Yokosaki et al, 1996). Epithelial