Squamous cell carcinoma antigen 1 and 2 expression in cultured normal peripheral blood mononuclear cells and in vulvar squamous cell carcinoma

Abstract

Squamous cell carcinoma antigen (SCCA) is expressed in normal squamous cell epithelia and in squamous cell carcinomas (SCC). Two nearly identical genes encode the inhibitory serpins SCCA1 (SERPINB3) and SCCA2 (SERPINB4). Serum levels of SCCA are elevated in patients with benign skin diseases and in patients with SCC. SCCA, used for the monitoring of SCC patients, presents no satisfactory diagnostic specificity. As we have shown previously, the reverse transcription polymerase chain reaction (RT-PCR)-based SCCA messenger RNA (mRNA) testing aimed at detecting disseminated cancer cells may be hampered by the false-positive results due to SCCA expression in activated peripheral blood mononuclear cells (PBMC). The aim of this study was to assess the expression of SCCA at mRNA and protein levels in cultured normal PBMC, compared to that in vulvar SCC (VSCC) samples. High SCCA concentrations were found in vulvar tumours and in metastatic lymph nodes, while negative inguinal lymph nodes from the same patients often presented significantly less SCCA. In normal activated PBMC, the level of SCCA protein was the lowest. At the mRNA level SCCA was detectable in normal PBMC even in cultures with no mitogen stimulation, but only by the nested RT-PCR, contrary to VSCC samples found to be SCCA positive already in one-step PCR. Both SCCA1 and SCCA2 transcripts were present in cultured PBMC; SCCA1 was expressed at a higher level than SCCA2. In conclusion, both SCCA forms are detectable in normal PBMC cultured in vitro. SCCA expression level in normal PBMC is much lower than in the squamous epithelium-derived cells. In VSCC, in addition to tumour itself, metastatic lymph nodes seem also to be a potential source of serum SCCA.

SERPINB3 is associated with longer survival in transgenic mice

“…The biological role of this serpin has not been yet completely defined. SB3 is physiologically expressed in squamous epithelia, in endothelial cells of the veins, in arteries walls9 and in peripheral blood mononuclear cells10. It is also overexpressed in neoplastic cells of epithelial origin1112.…”

Antiapoptotic serine protease inhibitors contribute to survival of allergenic T H 2 cells

“…However, Spi2A can be induced by IFN-γ in activated macrophages 43 and so it is possible that in different physiological settings IFN-γ may affect Th1 cell survival through Spi2A up-regulation. SCCA-1/SCCA-2 expression has been noted previously in human mononuclear cells 45 and intriguingly it has been reported that deficiency in mouse Serpinb3a , which is thought to be the homologue of human SCAA-1/SCAA-2, reduces airway hyper-responsiveness by limiting goblet cell hyperplasia 46 . In contrast to our findings with OVA-specific IgE levels in our Serpina3g (Spi2A) KO mouse, levels of HDM-specific IgG1 and IgE l were no different between Serpinb3a KO and wild-type mice 46 .…”

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

“…The over-expression of SCCA was initially described in many different cancers of epithelial origin such as head and neck, vulvar, lung and oesophageal tumors [13][14][15][16]. Recently Pontisso et al [17] detected SCCA expression in HCC by immunohistochemistry for the first time but the expression pattern of SCCA1 and SCCA2 in cancer pathogenesis is not fully defined.…”