Urologic Oncology: Seminars and Original Investigations
Original articleLaboratory—prostatePsoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells1,
Introduction
Psoriasin, also known as S100A7, is a member of S100 calcium binding proteins. It was first identified as a protein highly up-regulated in psoriatic epidermis [1]. To date, there are 21 S100 proteins identified in human, of which 17 are tightly clustered in a region of the human 1q21 chromosome [2], [3]. They are widely expressed in various cell types and are localized in the cytoplasm and/or nucleus of the cell and, in some cases, are found to be secreted. These calcium binding and signaling proteins are involved in the regulation of cell proliferation, apoptosis, differentiation, and migration. Aberrations of their expression and functions have been indicated in psoriasis, neurodegenerative disorders, and inflammatory diseases [4]. Certain S100 proteins have also been indicated in development and progression of malignancies [5].
Psoriasin differs from the other S100 proteins by its lack of calcium binding ability in 1 EF-hand at the N-terminus. In addition to its overexpression in the skin lesions of psoriatic patients, it is also up-regulated and excreted from cells in the epidermis during inflammation. Interestingly, psoriasin is a chemotactic factor for keratinocytes [6], [7] and leukocytes [8]. S100A7 has also been implicated as a prominent antimicrobial peptide (AMP) that selectively kills Escherichia coli on the surface of skin [9]. In addition to its role in the inflammatory process and infection, the relevance to cancer has been investigated together with other S100 proteins. Aberrant expression of psoriasin has been indicated in certain squamous cell and other solid tumors, including bladder, breast, oral, skin, head, and neck cancers [10], [11], [12], [13]. For example, the expression of psoriasin has been intensively examined in breast cancer and has been found to be up-regulated in both ductal carcinomas in situ and some tumors at advanced stages, particularly in estrogen receptor α (ERα) negative and ERβ positive tumors. The elevated expression level is associated with poor prognosis and survival in patients with breast cancer.
However, the expression of psoriasin in prostate cancer (CaP) and its impact on the functions of CaP cells remained unknown. The current study aimed to examine its implication in CaP.
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Materials and cell lines
The following human prostate cell lines were used: PC-3 (European Collection of Animal Cell Culture, Salisbury, UK); DU-145, LNCapFGC, CA-HPV-10, and PZ-HPV-7 (American Type Culture Collection, Manassas, VA); PNT-1A and PNT-2C2 were provided by Professor Norman Maitland (University of York, England, UK). The cells were maintained in Dulbecco's modified Eagle medium (DMEM)-F12 medium supplemented with 10% fetal calf serum and antibiotics. Other kits and reagents were purchased from
Expression of psoriasin in prostate cancer
The expression of psoriasin in CaP specimens was examined using immunohistochemical staining (Fig. 1). Intensive staining of psoriasin was seen in the cytoplasm of CaP cells in CaP specimens. The staining appeared to be relatively weak or absent from prostate epithelial cells from normal prostate tissues. Positive staining for psoriasin was seen in most of the CaP specimens (32/33), P = 0.003 in comparison with its expression in normal prostate tissues, in which only half of the normal prostate
Discussion
The present study examined the expression of psoriasin in both CaP tissues and CaP cell lines. Elevated expression of psoriasin was seen in CaP in comparison with normal prostate tissues. It has also been noticed that weak or negative staining of psoriasin was evident in both normal prostate and some foci of CaP with completely disrupted gland structure. These data collectively indicate that deregulation of psoriasin occurs in CaP, and that this molecule may play different roles at different
Conclusions
Psoriasin is expressed in prostate epithelia and cancer cells. Elevated expression of psoriasin is a common feature in CaP. Its expression in CaP cells is associated with cell survival, adhesion, and invasion. Psoriasin regulates invasion of CaP cells via MMPs. Its implications in tumorigenesis and disease progression of CaP warrant further investigations.
6.Acknowledgment
The authors gratefully acknowledge support for this work by Cancer Research Wales.
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Differential proteomic analysis of actinic keratosis, Bowen's disease and cutaneous squamous cell carcinoma by label-free LC–MS/MS
2018, Journal of Dermatological ScienceCitation Excerpt :We measured higher levels of S100A7 and CRABP2 proteins in BD compared to cSCC. Previous studies have also reported that S100A7 levels are increased in pre-invasive cSCC and decreased in invasive cSCC [46–48]. Studies on breast cancer cells [49] have suggested that S100A7 plays a tumor-suppressive role which is mediated through down-modulation of proto-oncogenes cyclin D1 and c-myc, levels of which were measured to be significantly lower in BD compared to cSCC [44,45].
An orthologue of the host-defense protein psoriasin (S100A7) is expressed in frog skin
2017, Developmental and Comparative ImmunologyCitation Excerpt :S100A7 is not only secreted by keratinocytes of the skin (Gläser et al., 2005; Madsen et al., 1991) but is also considered a principal E. coli-killing factor of the human tongue and the epithelium layer of the urogenital tract (Meyer et al., 2008; Mildner et al., 2010). Apart from being an important bactericidal protein, S100A7 also functions in skin differentiation, cancer, and as a chemotactic protein during inflammation (Hattori et al., 2014; Jinquan et al., 1996; Moubayed et al., 2007; Ye et al., 2013). Disulphide-reduced S100A7 acts as a broad-spectrum fungicide on human skin (Hein et al., 2015).
S100A8 as potential salivary biomarker of oral squamous cell carcinoma using nanoLC-MS/MS
2014, Clinica Chimica ActaCitation Excerpt :Immunohistochemical staining implied increment of salivary S100A8 derived from secreted proteins of OSCC tissues in OSCC patients. Previous reports demonstrated S100A7 overexpressing in tissues of oral lesions [45] as well as regulating invasion and growth of breast and prostate cancers [46,47]. Our study showed low increment of salivary S100A7 in OSCC cases at T1 stage as well as low expression of it in T1 stage tissues (Figs. 3 and 5).
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The authors dedicate this works to a colleague, the late Dr. Gaynor Davies (1967–2006).
The authors declare no conflict of interest.