Psoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells

doi:10.1016/j.urolonc.2012.05.006

Urologic Oncology: Seminars and Original Investigations

Volume 31, Issue 8, November 2013, Pages 1576-1583

https://doi.org/10.1016/j.urolonc.2012.05.006 Get rights and content

Abstract

Objectives

Psoriasin, also known as S100A7 and first identified as a protein highly expressed in psoriatic lesions, is a calcium binding protein that has been indicated in various malignancies. The current study aimed to examine the implication of psoriasin in prostate cancer (CaP), particularly its impact on functions of CaP cells.

Materials and methods

Expression of psoriasin was examined in a variety of prostatic cell lines and human CaP tissues using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Knockdown and overexpression of psoriasin in CaP cells was performed using specifically constructed plasmids, which either had an anti-psoriasin ribozyme transgene or the full-length human S100A7 coding sequence. The effects of manipulating psoriasin expression on cellular functions of CaP cells were assessed using in vitro assays.

Results

Psoriasin was expressed in prostate epithelia and cancer cells. Elevated expression of psoriasin was evident in CaP from its IHC staining in CaP frozen specimens. Psoriasin promoted cell survival under serum starvation. Its expression was inversely correlated with cell-matrix adhesion. Psoriasin increased invasiveness of PC-3 cells via a regulation of matrix metalproteinases (MMPs).

Conclusions

Aberrant expression of psoriasin is implicated in CaP. Its expression in CaP cells is associated with cell survival, adhesion, and in vitro invasion, which is via the regulation of MMPs.

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.

Section snippets

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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Multiple myeloma (MM) is a plasma cells neoplasm which is often preceded by a preneoplastic condition called monoclonal gammopathy of unknown significance (MGUS). A protein called High-mobility group box-1 (HMGB-1) controls transcription and genomic stability. Both pro- and anti-tumor properties of HMGB1 have been described during tumor growth. The S100 protein family includes a protein known as psoriasin. Poorer prognosis and survival were linked to higher psoriasin expression in cancer patients. The goal of the current investigation was to compare the plasma levels of HMGB-1 and psoriasin in patients with MM and MGUS significance, as well as in a group of healthy controls. According to our research, patients with MGUS have higher HMGHB-1 concentrations than healthy controls (846.7 ± 287.6 pg/ml vs. 176.9 ± 204.8 pg/ml for controls, p < 0.001). Similarly, we found a huge difference in HMGB-1 levels for MM patients with respect to controls (928.0 ± 551.4 pg/ml vs. 176.9 ± 204.8 pg/ml; p = 0.001). No difference was found as for the Psoriasin levels in the three groups considered. Additionally, we tried to evaluate the knowledge already present in the literature about putative mechanisms of action for these molecules in the onset and development of these disorders.
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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].
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2073 unique proteins were identified. cSCC had the highest number of differentially abundant proteins (63 proteins) followed by BD (58 proteins) and AK (46 proteins). Six proteins (APOA1, ALB, SERPINA1, HLA-B, HP and TXNDC5) were differentially abundant in cSCC compared to AK. Immunohistochemical analysis corroborated changes in MIF, RPL37A and TXNDC5. IPA analysis predicted that cell proliferation, angiogenesis and inflammatory reactions were significantly activated in cSCC compared to BD and AK. Cell death and DNA damage were predicted to be inhibited in BD.
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¹: The authors dedicate this works to a colleague, the late Dr. Gaynor Davies (1967–2006).

: The authors declare no conflict of interest.

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Original articleLaboratory—prostatePsoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells1,

Abstract

Objectives

Materials and methods

Results

Conclusions

Introduction

Section snippets

Materials and cell lines

Expression of psoriasin in prostate cancer

Discussion

Conclusions

6.Acknowledgment

J Invest Dermatol

Genomics

Eur J Surg Oncol

J Urol

Blood

Am J Pathol

Am J Pathol

Six S100 genes are clustered on human chromosome 1q21: Identification of 2 genes coding for the 2 previously unreported calcium-binding proteins S100D and S100E

Proc Natl Acad Sci U S A

Natural and amyloid self-assembly of S100 proteins: Structural basis of functional diversity

FEBS J

Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation

J Immunol

IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes

J Immunol

Chemotactic activity of S100A7 (psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15

J Immunol

Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection

Nat Immunol

RanBPM interacts with psoriasin in vitro and their expression correlates with specific clinical features in vivo in breast cancer

BMC Cancer

Psoriasin is aberrantly expressed in human breast cancer and is related to clinical outcomes

Int J Oncol

Original article
Laboratory—prostate
Psoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells1,