Psoriasin: Its other meaning and implications
By Warren R. Heymann, MD
May 28, 2018
Biologic processes are akin to world-class orchestras requiring precise coordination between the conductor and musicians. One miscue by either can spoil the performance. I am awed by how our bodies function magnificently in health. The orchestration of the panoply of proteins, enzymes, cytokines, hormones, et cetera, underscores the fact that even one aberrant molecule can have vast implications. To comprehend biologic effects, it is essential to focus on effects of individual proteins in health and disease, with the caveat that they are not functioning in isolation, but as part of the whole.
Psoriasin (S100A7 protein — not to be confused with the over-the-counter coal tar product) has been receiving increasing attention for its potential roles in dermatology and oncology.
According to Liu et al, “Psoriasin, also known as S100A7, is a member of the S100 protein family of calcium binding proteins and was first identified as being overexpressed in psoriatic skin lesions. It is a 11.4-kDa secretory protein encoded on chromosome 1q21, clustered alongside 16 other members of the S100 family within a region known as the epidermal differentiation complex (EDC). The S100 family encodes both cytoplasmic and secreted proteins that share EF-hand helix-loop-helix domains, important for their role as calcium binding proteins. Psoriasin S100 proteins are widely expressed in numerous cell types localised to the cytoplasm and/or nucleus, or in some cases are secreted. Due to their role in calcium binding and signaling, they are involved in numerous cell functions including proliferation, differentiation, migration and apoptosis. In addition to its overexpression in psoriatic skin lesions, aberrant Psoriasin expression has been implicated in a range of human diseases including cancer. Interestingly, Psoriasin is a chemotactic factor for keratinocytes and leukocytes, and is also upregulated and excreted from cells of the epidermis during inflammation. Additionally, Psoriasin has been implicated as an antimicrobial peptide, selectively killing E. coli on the surface of the skin. Therefore, Psoriasin may be utilised, via the host immune response, as a selective chemotactic factor both in psoriasis and cancer.” (1)
I was most intrigued by a study by Mitoma and Furue who examined the distribution of S100A7 in formalin-fixed, paraffin-embedded tissues from five cases of porokeratosis (3 DSAP, 1 DSP, and 1 porokeratosis Mibelli) and five cases of normal skin. The keratinocytes in normal skin did not stain for S100A7. In all porokeratoses, S100A7 was detected in the cytoplasm and nucleus of keratinocytes beneath and surrounding the cornoid lamella. The authors contend that coordinated expression of S100A7 is necessary for the correct terminal differentiation of keratinocytes, while overexpression of S100A7 leads to dysregulated keratinocyte differentiation. The upregulation of S100A7 may be an integral part of the pathomechanism-generating cornoid lamella in porokeratosis. (2)
In psoriasis, there is a gradient of psoriasin expression in the epidermis, with the highest expression in the suprabasal, differentiated layers. Psoriasin is strongly induced by IL-22, and by the combination of IL-17 and TNF-alpha. Psoriasin appears to mediate the expression of involucrin, desmoglein 1, transglutaminase 1, and CD24 in normal differentiation by interacting with various signaling proteins including the NF-ĸB regulator Jab1. Additionally, extracellular psoriasin binds to the receptor for advanced glycation end products (RAGE) promoting endothelial proliferation. (3) It has also been demonstrated that psoriasin expression is promoted by oxidative stress in keratinocytes, thereby amplifying the reactive oxygen species-induced expression of angiogenic factors relevant to psoriasis (VEGF, heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1). (4)
Psoriasin and koebnerisin (S100A15) may also be potential links between psoriasis and atherosclerosis. A statistically significant positive correlation was observed between intima-media thickness of the carotid arteries and PASI, serum psoriasin, and serum koebnerisin. (5) Targeted anti-Psoriasin therapy could theoretically benefit psoriatic lesions and associated comorbidities.
Most importantly, increased expression of Psoriasin has been described in cancers from several tissues (lung, breast, skin, bladder, head and neck, larynx, esophagus, stomach and ovary), with strong correlation to poor prognosis. Along with other S100 proteins, Psoriasin is involved in processes such as calcium homeostasis, cell movement, proliferation and differentiation, through the interaction with cytoskeletal proteins and transcription factors that correlate with tumor growth, angiogenesis, and metastatic potential. Experimental monoclonal antibodies resulting in S100A7 blockade have inhibited tumor growth and prevented metastasis in mice. (6)
I will no longer think of Psoriasin as just crude coal tar. Its other definition (S100A7) may have far more profound effects.
1. Liu Y, et al. Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression. Int J Oncol 2017; 50: 1491-1500.
2. Mitmoma C, Furue M. Overexpession of S100A7 protein is an integral part of abnormal epidermal differentiation in cornoid lamella of porokeratosis. Int J Dermatol 2018; 57: e7-e9.
3. Ekman A-K, et al. Overexpression of psoriasin (S!))A7) contributes to dysregulated differentiation in psoriasis. Acta Derm Venereol 2017; 97: 441-8.
4. Vegfors J, et al. Psoriasin (S100A7) promotes stress-induced angiogenesis. Br J Dermatol 2016; 175: 1263-73.
5. Awad SM, et al. Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis. Clin Exp Dermatol 2018; 43: 262-7.
6. Padilla L, et al. S100A7: From mechanism to cancer therapy. Oncogene 2017; 36: 6749-61.
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