Novel binders derived from an albumin-binding domain scaffold targeting human prostate secretory protein 94 (PSP94)
Abstract
Prostate secretory protein 94 (PSP94), also known as β-microseminoprotein, is a product of the MSMB gene and one of the most abundant proteins found in human seminal plasma (Anklesaria et al., 2013). This small cysteine-rich non-glycosylated protein is considered to be involved in regulation of many biological processes including male reproduction.
It has been observed that PSP94 and its porcine homologue inhibit acrosomal reaction, sperm motility, and maintain the sperm environment (Anahi Franchi et al., 2008; Manaskova-Postlerova et al., 2011). Despite of its possible role in reproduction, recently it has been proposed its association with development of prostate cancer (PC).
It has been demonstrated that PSP94 suppresses tumor growth and reduces proliferation of some cancer cells by inducing apoptosis. This action is suggested to be regulated via binding to cell-surface receptors (Yang et al., 1998; Annabi et al., 2006).
Moreover, the large genome-wide association studies showed that decreased expression of PSP94 caused by the rs10993994 single nucleotide polymorphism is associated with an increased risk of developing prostate cancer, suggesting a protective role of PSP94 in PC incidence (Lou et al., 2009; FitzGerald et al., 2013). Currently, the clinically validated test for PC diagnosis relies on detection of serum level of prostate-specific antigen (PSA, human kallikrein-3) using monoclonal antibody-based ELISA kit but this examination, yet widely used, fails to predict early stages of PC development and, in addition, does not distinguish precisely between malign form of PC and benign prostate hyperplasia.
Due to lack of this specificity many patients have to undergo unnecessary prostate tissue biopsy (Lazzeri et al., 2012).