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A Novel Marker for Basal (Stem) Cells of Mammalian Stratified Squamous Epithelia and Squamous Cell Carcinomas¹

Department of Immunology, University of Alberta, Edmonton, Alberta T6G 2H7 [J. S., B. M. L.]; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8 [A. A. N.]; Department of Laboratory Medicine, Grey Nuns Hospital, Edmonton, Alberta T6L 5X8 [D. J. W.]; BIOMIRA, Inc., Edmonton, Alberta T6N 1E5 [A.A.N., G.S.B., B.M.L.]; and Department of Veterinary Pathology, Western College of Veterinary Medicine, Saskatoon, Saskatchewan S7N 0W0 [D. M. H.], Canada

We have developed a monoclonal antibody (174H.64) which selectively recognizes antigens shared by the basal cells of mammalian stratified squamous epithelium and squamous cell carcinoma (SCC). Histopathological studies of the frozen tissue sections demonstrated selective binding of this antibody to SCCs of human, bovine, canine, feline, and murine origin. Tumors of other histological types did not show reactivity with the antibody. In well-differentiated SCCs the peripheral layer of the tumor showed preferential binding of the antibody, suggesting that the antigens are associated with the proliferative compartment of the tumor. Studies on normal human tissues showed selective binding of the antibody to the basal layer of stratified squamous epithelia, thymic epithelial cells, and myoepithelial cells around breast ducts, while no antibody binding was observed for the suprabasal layers of stratified epithelia, simple epithelia, or tissues of nonepithelial origin. A similar pattern of antibody binding was also observed for bovine and murine skin with staining of the basal layer. The antigens detected by monoclonal antibody 174H.64 were characterized from cytoskeletal protein extracts of normal human keratinocytes as well as human and bovine SCC tissues by using an immunoblotting technique. The antigens detected in normal human keratinocytes consisted of two major protein bands of approximate molecular weights of 48,000–50,000 and 57,000. In bovine SCC tumor the antigen detected was the M_r 48,000–50,000 band and in the human SCC tumor it was the M_r 57,000 band. A murine lung SCC model was developed with a murine SCC cell line KLN-205. The lung tumor obtained was reactive against the antibody and showed selective staining of the peripheral layer of the tumor containing the stem cell population. The antigens described by monoclonal antibody 174H.64 appear to be molecules associated with the stem cell populations of normal stratified epithelium and squamous cell carcinoma.

¹ This work was supported by a grant from the Medical Research Council of Canada and by BIOMIRA, Inc., Edmonton, Alberta, Canada.

² Supported by an Alberta Heritage Foundation for Medical Research Fellowship.

³ To whom requests for reprints should be addressed.

Received 11/ 7/88. Revised 1/31/89. Accepted 2/ 7/89.