Co-expression of the squamous cell carcinoma antigens 1 and 2 in normal adult human tissues and squamous cell carcinomas

Squamous cell carcinoma antigen (SCCA) serves as a serological marker for a dvanced squamous cell carcinomas (SCCs) and as an indicator of therapeutic response. Recent molecular studies show that the SCCA is transcribed by two almost identical tandemly arrayed genes, SCCA1 and SCCA2. These genes are members of the high molecular weight <(ser)under bar>ine <(pr)under bar>ote inase <(in)under bar>hibitor (serpin) superfamily. Although SCCA1 and SCCA2 are 92% identical at the amino acid level, they have distinct biochemical properties. Paradoxically, SCCA1 is an inhibitor of papain-like cysteine pr oteinases, such as cathepsins L, S, and K, whereas SCCA2 inhibits chymotryp sin-like serine proteinases, cathepsin G, and mast cell chymase. Using a ne w set of discriminatory monoclonal antibodies (MAbs) and polymerase chain r eaction (PCR) assay, we showed that SCCA1 and SCCA2 were co-expressed in th e suprabasal layers of the stratified squamous epithelium of the tongue, to nsil, esophagus, uterine cervix and vagina, Hassall's corpuscles of the thy mus, and some areas of the skin. SCCA1 and SCCA2 also were detected in the pseudo-stratified columnar epithelium of the conducting airways. Examinatio n of squamous cell carcinomas of the lung and head and neck showed that SCC A1 and SCCA2 were co-expressed in moderately and well-differentiated tumors . Moreover, there was no differential expression between these SCCA "isofor ms" in normal or malignant tissues. In contrast to previous studies, these data indicated that the expression of SCCA1 and SCCA2 was not restricted to the squamous epithelium and that these serpins may coordinately regulate c ysteine and serine proteinase activity in both normal and transformed tissu es.