Co-expression of the Squamous Cell Carcinoma Antigens 1 and 2 in Normal Adult Human Tissues and Squamous Cell Carcinomas

Abstract

SUMMARY Squamous cell carcinoma antigen (SCCA) serves as a serological marker for advanced 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 serine proteinase inhibitor (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 proteinases, such as cathepsins L, S, and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, cathepsin G, and mast cell chymase. Using a new set of discriminatory monoclonal antibodies (MAbs) and polymerase chain reaction (PCR) assay, we showed that SCCA1 and SCCA2 were co-expressed in the suprabasal layers of the stratified squamous epithelium of the tongue, tonsil, esophagus, uterine cervix and vagina, Hassall's corpuscles of the thymus, and some areas of the skin. SCCA1 and SCCA2 also were detected in the pseudo-stratified columnar epithelium of the conducting airways. Examination of squamous cell carcinomas of the lung and head and neck showed that SCCA1 and SCCA2 were co-expressed in moderately and well-differentiated tumors. Moreover, there was no differential expression between these SCCA "isoforms" 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 cysteine and serine proteinase activity in both normal and transformed tissues.

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

“…cathepsin G and mast cell chymase; Schick et al, 1997). Previously, SCCA1 and 2 have been reported to be coexpressed in moderately-and well-differentiated squamous cell carcinomas of the lung and head and neck, with no differential expression of the two transcripts between normal and malignant tissue (Cataltepe et al, 2000). Conversely, Kishimoto et al (2001) describe the over-expression of SCCA1 and 2 in an adenoid squamous cell carcinoma cell line derived from the maxillary sinus.…”

SERPINB11 Is a New Noninhibitory Intracellular Serpin

“…cDNA Isolation and DNA Sequencing-The SERPINB11 cDNA was amplified from prostate and lung first-strand cDNAs (Clontech) using specific primers (forward 1, 5Ј-ATGGGTTCTCT-CAGCACAGCTAAC-3Ј; reverse 1, 5Ј-GAGGTGTGAACAG-CTTTTTGG-3Ј) as described (19). A heminested PCR was performed using the cDNA templates from first-round PCR with forward 1 and reverse 2 primers (reverse 2, 5Ј-CATCTG-CAACTCTGAGCCTTG-3Ј).…”

“…Tissue Expression Survey-First-strand cDNA samples from human adult tissues (multiple tissue cDNA panels; Clontech) were assayed by PCR for SERPINB11 transcripts using specific primers (forward 2 (5Ј-AAGCAGCTGAATTCGGGG-ACG-3Ј) and reverse 2 (see above)) that amplified a 490-bp product (19). To control for template integrity, cDNA samples were assayed for a 616-bp ␤-actin fragment (forward primer, 5Ј-CCTCGCCTTTGCCGATCC-3Ј; reverse primer, 5Ј-GGATCTTCATGAGGTAGTCAGTC-3Ј).…”

SERPINB12 Is a Novel Member of the Human ov-serpin Family That Is Widely Expressed and Inhibits Trypsin-like Serine Proteinases

“…The size of the nested PCR product was 527 bp. To control for integrity of the starting cDNA templates, samples were assayed for a 616-bp ␤-actin (ACTB) fragment (forward primer, 5Ј-CCTCGCCTTTGCCGATCC-3Ј; reverse primer, 5Ј-GGATCTTCAT-GAGGTAGTCAGTC-3Ј) as described previously (16).…”