Spermatozoa are hidden from the immune system by the presence of the blood–testis barrier, which prevents immunoglobulins and immunocompetent cells from entering the lumen of the seminiferous tubules. The protection provided by the blood–testis barrier is, however, incomplete. It has been known for a long time that antisperm antibodies (ASAs) against human spermatozoa from immunologically infertile men can spontaneously appear [82, 83]. The targets of ASAs have been antigens on spermatozoa, and the antibodies can be detected in semen either bound to spermatozoa  or free in the seminal plasma . Additionally, these antibodies can be present in blood serum of both men and women . The prevalence of ASAs in infertile couples (both men and women) has been reported to vary between 9% and 36% depending on the study centre [87, 88]. It appears that, in vital spermatozoa, only those ASAs that bind to the sperm membrane will be of functional relevance and their binding sites will be crucial for fertility and viability .
Antisperm antibodies may decrease fertility by inhibiting sperm transport and/or gamete interactions . ASAs can cause the agglutination of spermatozoa and thereby prevent sperm motility , impair penetration of the cervical mucus , block capacitation, the acrosome reaction  and binding to the zona pellucida  and obstruct sperm–oocyte fusion . We found somewhat unexpectedly that ASAs recognize not only sperm membrane proteins but also prostasomes . We also found very high frequency of recognition of prostasomes as antigens by circulating human ASAs from immunoinfertile men and women . Also, polyclonal antibodies raised against prostasomes resulted in the agglutination of a high percentage of human spermatozoa displaying several types of formation in a similar fashion to that seen in immunologically infertile patients with demonstrable ASAs . As a result of these findings, prostasomes provide a new category of sperm antigens with interesting implications for studies of the mechanism(s) involved in ASA-mediated infertility and immunological control of fertility.
Several prostasome antigens serving as targets for ASAs have been identified, and unexpectedly, they mostly differed from those identified in spermatozoa [98, 99]. The most frequently occurring prostasomal antigens were prolactin-inducible protein (PIP) and clusterin . The observations that prostasomes can act as sperm surface antigens and that most immunoinfertile men have sperm-agglutinating ASAs recognizing prostasomes add further complexity to the problem of immunological infertility. Still, the uneven allocation of prostasomal antigens as targets for ASAs (predominantly PIP and clusterin) could be of interest with regard to fertility regulation. Both antigens are glycoproteins, meaning that they may display different post-translational modification patterns, perhaps giving rise to different isoforms and antibody responses. This in turn increases the possibility of finding unique antibodies against these prostasome glycoproteins relevant to infertility. The recognition of such antigens may also be important for potential immunocontraceptive efforts.
Prostate cancer is the most common cancer amongst men older than 50 years in western societies , and the incidence is increasing steadily in countries in general. The causes of prostate cancer are essentially unknown. Nevertheless, several factors have been connected with a higher risk of this disease. These factors include increasing age, family history of prostate cancer, living in western countries and race (prostate cancer is especially common in African-American men) . In addition, the increasing incidence of prostate cancer affects those who have migrated from low-risk to high-risk countries . Androgen stimulation may be a carcinogenic factor, as testosterone promotes proliferation of prostate epithelial cells and prevents apoptosis . Prostate cancer is extremely rare in men castrated before puberty .
Primary cancer in the seminal vesicles is extremely rare , in contrast to the very high incidence of cancer in the prostate gland. This deserves attention because the two types of glands represent neighbouring anatomical locations, and both are exocrine accessory genital glands under similar hormonal control. This discrepancy prompted us to think in terms of the prostasome being an accessory to the development of prostate cancer, because the secretion of seminal vesicles is devoid of prostasomes and prostasome-like structures . It is noteworthy that not only normal prostate acinar secretory cells but also neoplastic prostate cells and even poorly differentiated prostate cancer metastases are able to synthesize and export prostasomes to the extracellular space [14, 108, 109].
It has long been known that tumour cells tend to exploit opportunistically the host′s physiological system to obtain support in terms of nutrition, growth and metastasis. We proposed some years ago that several attributes of the prostasome, primarily developed to sustain the fertilizing spermatozoa, can also promote the transition from a normal to a neoplastic prostatic cell and help the prostasome-producing, poorly differentiated cancer cell to survive and proliferate in a primarily hostile environment . The control of cell proliferation, differentiation and signal transduction pathways is generally mediated by protein kinases and phosphatases [111–113], whose actions are modified by hormones, growth factors and mitogens [112, 114]. Hence, the phosphorylation of a protein is carried out by protein kinases, which can be subdivided into two main categories depending on the acceptor amino acid of the transferred phosphoryl group: hydroxy (OH) groups on serine/threonine residues and phenolic groups on tyrosine residues of their respective proteins. The serine/threonine protein kinases are generally second messenger (e.g. cyclic AMP) dependent. Protein kinases that phosphorylate the tyrosine-containing protein residue include hormone receptor-associated kinases. Protein phosphorylation is controlled reversibly by phosphoprotein phosphatases that cleave the phosphoryl group from the acceptor amino acid facilitating a phosphorylation/dephosphorylation cycle. Approximately half of the protein kinase activity in prostatic fluid is associated with prostasomes [115, 116], and co-incubation of spermatozoa and prostasomes was shown to result in a 10-fold increase in total protein phosphorylation compared to the level of phosphorylation achieved through incubation with either component alone . This finding supports the interactive relationship between prostasomes and spermatozoa, even though they have different origins in the genital apparatus.
Our studies on prostasomes derived from different types of prostate cancer cells revealed distinctly upregulated protein kinase (A and C) and casein kinase activities compared to normal seminal prostasomes . This enhanced protein kinase activity of cancer cell-derived prostasomes may participate in the self-defence programme of prostate cancer cells against attack by the complement system. The main event in the activation of complement is proteolytic cleavage of C3, producing C3a and C3b. Two enzyme complexes (convertases), which are assembled by three different activation pathways, accomplish the cleavage. These converge in a common pathway, forming the MAC (C5b–C9), which elicits cell lysis by insertion into the lipid bilayer of plasma membranes. Complement activation on autologous cells is controlled by several soluble and membrane-bound regulators. The role of complement activation as a mechanism for destruction of malignant cells is not yet well understood. However, it is highly probable that the complement system is involved in control of malignant tumours, as these cells are extremely sensitive to altered self- and nonself-structures on cell surfaces . It is therefore assumed that cells that are unable to protect themselves against complement attack will be eliminated early in the process of cancer development. It was reported that phosphorylation of complement component C3 made it inaccessible to physiological activation . Our findings demonstrated that upregulated protein kinase A of cancer-derived prostasomes was indeed able to phosphorylate complement component C3 . We therefore believe that these cancer cell-derived prostasomes have the ability to disarm complement activation by regulatory phosphorylation. Additionally, CD59 expression was higher in prostasomes from cancer cells than in those from normal cells . CD59 could be transferred, functionally active, from prostasomes to other cells including prostate cancer cells, thereby inhibiting complement-mediated lysis . Thus, prostate cancer cells with the support of their prostasomes have two mechanisms of survival against the host complement system.
It has been suggested that fibrinogen plays a role to induce migration of tumour cells and is associated with an infiltrative histological phenotype in bladder cancer . We found that fibrinogen was phosphorylated by all three types of protein kinases (A, C and casein kinase) of malignant cell-derived prostasomes . This is interesting in the light of the findings that phosphorylated fibrinogen is more resistant to cleavage  and that suppression of fibrinolysis is important for metastatic prostate cancer cells.
Patients with prostate cancer as well as other types of cancer experience a much higher than expected incidence of thromboembolic events; this is commonly referred to as Trousseau’s syndrome. Although this association is well documented, the aetiology of the hypercoagulable state has remained obscure. Tissue factor (CD142), serving as a receptor and essential cofactor for factors VII and VIIa of the coagulation cascade, is the principal initiator of both coagulation and thrombosis . It is present in huge amounts in prostasomes . Prostasomes derived from different human prostate cancer cell lines overexpress and are able to phosphorylate tissue factor [125, 126]. Tissue factor is also known to support cancer growth and proliferation, including the promotion of tumour angiogenesis [123, 127], cell adhesion , cell migration  and tumour cell invasion . In addition, it binds with high affinity to plasminogen , an effector that may be involved in the enhancement of tumour growth and metastasis . Therefore, prostasomes by virtue of their high levels of tissue factor may play an active role in prostate cancer proliferation.
The clotting ability of prostasomes, seemingly in a dose-dependent fashion, may be related to their level of expression of tissue factor [126, 133]. However, no difference in plasma level of soluble tissue factor between patients with prostate cancer and controls has also been reported . Recent data support the view that prostate cancer patients with aggressive disease do have circulating prostasomes with membrane-bound tissue factor in their peripheral blood  and, therefore, circulating prostasomes may be the underlying cause of Trousseau’s syndrome in aggressive prostate cancer.