High Expression of Osteopontin and CD44v6 in Odontogenic Keratocysts

Abstract

Odontogenic keratocysts (OKCs) are more aggressive and more osteolytic lesions than dentigerous cysts (DCs) and radicular cysts (RCs). Osteopontin (OPN) is related to cancer metastasis and bone destruction. Binding of OPN to its cell membrane receptors integrin alphav and CD44v6 can enhance tumor cell motility, migration, invasion and spread. This study assessed the possible contribution of OPN, integrin alphav and CD44v6 to the local aggressive behavior and osteolytic ability of OKCs. We used an immunohistochemical method to examine the expression of OPN, integrin alphav and CD44v6 in tissue sections of 20 OKCs, eight DCs and 10 RCs. We found strong cytoplasmic OPN immunostaining in lining epithelial cells of 8 of 20 OKCs but not in any DCs and RCs. Positive OPN staining was also noted in the subepithelial connective tissue of four OKCs with intraepithelial expression of OPN. Diffuse and strong membranous integrin alphav staining was discovered in osteoclasts in all our tissue sections and in nearly all lining epithelial cells of DCs and RCs, but not in OKCs. In addition, diffuse and strong membranous CD44v6 staining was also observed in nearly all lining epithelial cells of OKCs, DCs and RCs. Binding of OPN to osteoclast cell membrane receptor integrin alphav can activate the osteoclasts and increase their osteolytic activity. In addition, binding of OPN to OKC lining epithelial cell membrane receptor CD44v6 can enhance the motility, migration, invasion and spread of lining epithelial cells into the surrounding cancellous bone. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of OKCs in the jawbone can be explained at least partially by high expression of OPN and CD44v6 in lining epithelial cells of OKCs and high expression of integrin alphav in osteoclasts.