Alteration of integrin expression relates to malignant progression of human papillomavirus-immortalized esophageal keratinocytes

To investigate cellular changes related to the malignant progression of keratinocytes, we studied the serum-resistant clones from CHEK-1, a human papillomavirus type 16 E6/E7-immortalized esophageal cell line cultured in a serum-free medium. Established clones exhibited morphologic variety. Slow growing clones presented in cuboidal shapes with tight cellular adhesion and highly expressed α2 and α6β4 integrins. Moderately proliferating clones showed loose intercellular adhesion and reduced expression of α2 integrin. Spindle-shaped, rapidly proliferating clones with prominent actin stress fibers demonstrated reduced α6 and α4 integrin expression in addition to α2 integrin and showed anchorage-independent growth. Reduced expression of α2 integrin was observed between 50 and 100 population doubling lengths (PDLs) during the immortalization of CHEK-1. These results suggest that the reductions of α2 and α6β4 integrins are related to changes seen during immortalization and malignant progression.