Seminal Fluid Characterization for Male Fertility and Prostate Cancer: Kallikrein-Related Serine Proteases and Whole Proteome Approaches

Abstract

The kallikrein-related ( KLK) protease gene family encodes a subgroup of 15 serine proteases that includes prostate-specific antigen (PSA) or KLK3, the well-known biomarker for prostate cancer. PSA is also a major component of seminal fluid. To date, 10 other KLK serine proteases have been documented as present in seminal fluid (KLKs 1, 2, 4, 5, 6, 8, 10, 11, 13, and 14) and, like PSA, have the potential to contribute to male fertility, either directly or indirectly, by means of their proteolytic activity on seminal coagulum proteins. These KLK enzymes arise predominantly from the glandular epithelium of the prostate and are secreted into the lumen of the prostatic ducts that empty into the urethra upon ejaculation. Given their prostatic origin, they are also being considered increasingly as diagnostic/prognostic targets for prostate cancer. This article reviews the literature on seminal fluid PSA and more recent reports on the detection of other KLKs enzymes in this milieu, and their potential roles in male fertility and prostate cancer. We also discuss recent efforts to determine the proteomic profile of seminal fluid to identify new biomarkers for prostate disease.

Unleashing the therapeutic potential of human kallikrein-related serine proteases

“…KLK3 expression is restricted to the prostate and hence it is also known as the prostate-specific antigen (PSA). In normal prostate physiology, KLK3 cleaves fibronectin and the seminal-gel-forming proteins semenogelin 1 and semenogelin 2, leading to semen liquefaction and enhanced sperm motility [109][110][111][112][113] (FIG. 3a).…”

Zinc α2-Glycoprotein: A Multidisciplinary Protein

“…They have also shown that this observation is similar to that of breast cancer, where the loss of ZAG production was associated with the lack of tumor differentiation. It is interesting to note that the expression of ZAG in prostate cancer is similar to that of other relevant prostatic proteins (57), such as prostate-specific antigen and prostatic acid phosphatase, which are significantly decreased in prostatic tumors (63)(64)(65). Moreover, immunohistochemical studies assured the partial loss of ZAG expression in prostatic tissue after malignant transformation (47).…”

Prostasomes: extracellular vesicles from the prostate

“…Prostatic fluid accounts for 20-30% of seminal volume and contains high concentrations of citric acid, zinc and specific enzymes. Two major ones are prostate acid phosphatase (PAP) and prostate-specific antigen (PSA) (Veveris-Lowe et al 2007, Graddis et al 2011. The major function of the protease PSA is to liquefy the semen coagulum, although PSA has become better known as a biomarker for prostate cancer (Tosoian & Loeb 2010).…”