IDENTIFICATION OF A CELL-SURFACE PROTEIN WITH A ROLE IN STIMULATING HUMAN KERATINOCYTE PROLIFERATION, EXPRESSED DURING DEVELOPMENT AND CARCINOGENESIS

In an attempt to define cell surface molecules with an important role in the development of squamous cell carcinomas (SCCs), we generated mo noclonal antibodies (MoAbs) to a human keratinocyte cell line (FEP18-1 1-T1) capable of giving rise to SCCs in nude mice, MoAb 10G7 was selec ted for further study because it bound to a cell surface component pre ferentially expressed by this cell line as compared with normal human foreskin keratinocytes. This MoAb recognizes a cell surface protein (1 0G7 antigen) that is not detectable on normal keratinocytes in the for eskin in vivo, but whose expression is induced when the keratinocytes are dissociated from this tissue and placed in culture, Interestingly, the 10G7 antigen is downregulated upon keratinocyte differentiation i n in vitro. Consistent with its expression in hyper-proliferative epit helia in vitro, 10G7 antigen exhibited a classic oncofetal pattern of expression in vivo. Thus, although no reactivity was obtained with MoA b 10G7 in the epithelia of normal foreskin or cervical tissue, strong reactivity was detected in epithelia from genital lesions ranging from benign warts to invasive SCCs, Epidermis from developing fetal tissue also exhibited strong reactivity with MoAb 10G7. We have been able to demonstrate that this MoAb is capable of stimulating FEP18-11-T1 kera tinocyte proliferation in vitro in a concentration-dependent manner in the absence of growth factors, suggesting that the 10G7 antigen may p lay an important role in regulating cellular proliferation during deve lopment and in carcinogenesis in epithelial tissues.