Overexpression of Serpin Squamous Cell Carcinoma Antigens in Psoriatic Skin

Abstract

Squamous cell carcinoma antigen belongs to the serpin family and is used for the diagnosis and management of squamous cell carcinoma. We investigated the involvement of squamous cell carcinoma antigen in psoriasis, as it is always detected in the sera of patients with psoriasis. Squamous cell carcinoma antigen localization in psoriatic epidermis varied depending on its concentration in the patient's sera. When its level was low in serum, weak and scattered staining was observed in the granular layer. With a high concentration of squamous cell carcinoma antigen, strong staining through the suprabasal to granular layer and condensed staining around the plasma membrane or intracellular space was detected in the affected epidermis. Interestingly, squamous cell carcinoma antigen was abundant in nuclei of the granular layer cells and elongated rete ridges. Immunoelectron microscopy confirmed the localization of squamous cell carcinoma antigen in the nuclei as well as in the periphery of the cell membrane. A cDNA library was constructed from psoriatic epidermis and both clones, SCCA1 and SCCA2, were obtained. Attempts to raise specific antibodies or to prepare cRNA probes for SCCA1 and SCCA2 were unsuccessful because of their nearly identical structures. A primer pair from each reactive site sequence enabled us to give a distinctive product for SCCA1 and SCCA2 by reverse transcription polymerase chain reaction. Analysis using these primers demonstrated that the SCCA2 transcript was specifically expressed in psoriatic skin tissues. Our results suggest that overexpression of squamous cell carcinoma antigens is associated with the disease activity of psoriasis.

Maspin expression in normal skin and usual cutaneous carcinomas

“…Moreover, sweat gland basal cells were consistently decorated by maspin, both in nuclear and cytoplasmic compartments. These observations are in accordance with the findings of Takeda et al [30], who analyzed the expression SCC antigens 1 and 2 in psoriatic skin samples using conventional immunohistochemistry and immunoelectron microscopy and found that these serpins are abundantly expressed in the nuclei of the granular layer cells and of keratinocytes of elongated rete ridges [37]. Moreover, ovalbumin, another serpin, may also present a nucleocytoplasmic distribution [4].…”

New Horny Layer Marker Proteins for Evaluating Skin Condition in Atopic Dermatitis

“…SCCA1 inhibits papain-like cysteine proteinases such as cathepsins K, L and S [22, 23], while SCCA2 inhibits chymotrypsin-like serine proteinases such as cathepsin G and mast cell chymase [24]. Past studies have suggested that SCCAs may be involved in psoriasis and AD, probably as proteinase inhibitors [25, 26]. The mRNAs of SCCA1 and SCCA2 are highly expressed in the involved skin of AD patients, and the Th2-type cytokines IL-4 and IL-13 – but not the Th1-type cytokines IFN-γ or TNF-α – induce expression of SCCAs in cultured keratinocytes [26].…”

Serum Squamous Cell Carcinoma Antigen in Psoriasis: A Potential Quantitative Biomarker for Disease Severity

“…It has been reported that the serum level of SCCA was elevated in patients with atopic dermatitis [5], asthma [6], and psoriasis [7, 8], as well as in those with squamous cell carcinoma. The expression of SCCA was increased in both serum and skin in the psoriasis patients [9]. To clarify the clinical significance of SCCA in psoriasis, in this pilot study, we analyzed the SCCA levels in the serum of patients with psoriasis before and after a tumor necrosis factor-α (TNF-α) inhibitor, adalimumab treatment, and the association between the SCCA levels and clinical severity.…”