Abstract
Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various kinds of squamous cell carcinomas. Recently, our understanding of the underlying mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover, it has been shown that SCCA1/2 are involved in the pathogenesis of several inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD). IL-22 and IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13, signature cytokines of type 2 inflammation, both of which are positively correlated with the pathogenesis of psoriasis and allergic diseases, respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or keratinocytes, leading to high expression of SCCA1/2 in these diseases. Based on these findings, several trials have been performed to examine the potential of applying SCCA1/2 to biomarkers for these diseases. The findings show that SCCA2 is useful to aid diagnosis, estimate clinical severity and disease type, and assess responses to treatment in psoriasis and AD. These results suggest that SCCA2 has emerged as a novel biomarker for skin inflammatory diseases.
Highlights
Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4) are members of the ovalbumin serpin/clade B serpin family [1] and were originally discovered as tumor-specific antigens in the uterine cervix [2]
Suminami et al previously demonstrated that overexpression of SCCA1 in several kinds of tumor cells protected against apoptosis induced by an anti-cancer drug (7-ethyl-10-hydroxycamptothecin), by TNF-α, and by IL-2–activated natural killer (NK) cells, whereas silencing SCCA1 increased sensitivity to apoptosis induced by an anti-cancer drug and by TNF-α [4]
We found that SCCA1, but not SCCA2, potently inhibited various cysteine proteases derived from parasites Leishmania mexicana, Trypanosoma cruzi, Trypanosoma brucei rhodesience, and Fasciola hepatica
Summary
Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4) are members of the ovalbumin serpin (ov-serpin)/clade B serpin family [1] and were originally discovered as tumor-specific antigens in the uterine cervix [2]. SCCA1 and SCCA2 are highly homologous proteins, 91% identical at the amino acid level, and probably evolving from a common ancestor gene [1]. SCCA molecules are used as tumor markers for various kind of squamous cell carcinomas—esophagus, lung, head and neck, anal canal, and uterine cervix—reflecting tumor stage, tumor size, stromal invasion, lymph-vascular space status, and lymph node status [3].
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