Expression of αvβ6integrin in oral leukoplakia

Abstract

SummaryThe distribution of α v β 6 integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β 1 , β 3 , β 4 , β 5 , fibronectin and tenascin were also studied. The integrin α v β 6 was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. α v β 6 integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β 4 at the cell surface facing the basement membrane of all specimens. The integrins β 3 and β 5 were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both α v β 6 -positive and α v β 6 -negative tissues. A group of 28 leukoplakia patients were followed 1-4 years after first diagnosis. In this group, initially α v β 6 integrin-positive leukoplakia specimens had high tendency for disease progression while α v β 6 -negative specimens did not progress. These results suggest that the expression of α v β 6 integrin could be associated in the malignant transformation of oral leukoplakias.

Binding of TGF-β1 latency-associated peptide (LAP) to αvβ6 integrin modulates behaviour of squamous carcinoma cells

“…De novo expression of avb6 is seen in a number of epithelial malignancies, particularly oral squamous cell carcinoma (SCC) (Breuss et al, 1995;Jones et al, 1997;Hamidi et al, 2000;Ahmed et al, 2002). Expression of this integrin is often higher at the invasive front, supporting the contention that avb6 is capable of playing an active role in tumour progression.…”

“…Expression of avb6 is not detectable on keratinocytes in adult oral epithelium or epidermis. However, several studies have found high expression of avb6 in oral squamous cell (and other carcinomas), suggesting that this integrin may play a role in tumour progression (Breuss et al, 1995;Jones et al, 1997;Arihiro et al, 2000;Hamidi et al, 2000;Ahmed et al, 2002).…”

Integrin Regulation of Epidermal Functions in Wounds

“…8,98-100 However, both a v b 6 and a v b 5 are upregulated during wound healing, 8,[98][99][100] where each may bind to several ECM ligands through the arginine-glycine-aspartate (RGD) motif (e.g., fibronectin, tenascin, vitronectin). 3,40 Given the diversity of ligands that a v integrins can bind, their upregulation in wound epidermis may be important for modulating keratinocyte motility over the complex matrix of the wound bed.…”

Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the β6 integrin subunit

“…[2][3][4] Within the ␣v subfamily, the ␣v␤6 integrin is either not expressed or expressed at low levels in normal adult epithelia; however, it becomes highly expressed during tumourigenesis. 5,6 For example, induction of ␣v␤6 expression in oral leukoplakia appears to be a necessary prerequisite for progression to squamous cell cancer 7 and de novo expression of ␣v␤6 has been observed in oral squamous and colon cancers. 8,9 In lung cancer, approximately 50% of tumours exhibit upregulation of the ␣v␤6 subunit, 10 and in breast cancer ␣v␤6 expression has recently been linked to more advanced tumours.…”