The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

Abstract

Prostasomes are submicron secretory granules synthesized, stored and secreted by the epithelial cells of the human prostate gland. They are membrane-surrounded also in their extracellular appearance and the membrane architecture is composite. They are believed to be life-giving and act as protectors of the spermatozoa in the lower and upper female genital tract on their way to the ovum. Hence, the prostasomes are immunosuppressive and inhibitory of complement activation. Further, they promote sperm's forward motility and have antioxidant and antibacterial capacities. The prostasomes with their many composite abilities seem to turn against the host cell after the age of 50 y being conducive to the transition of the normal prostate epithelial cell into a neoplastic cell and therewith lay the foundations of the very high prevalence of prostate cancer of men of more than 50 y of age. Prostate Cancer and Prostatic Diseases (2004) 7, 21-31. doi:10.1038/sj.pcan.4500684 Keywords: prostasomes Prostate cancerProstate cancer is the most common cancer in men in Europe, North America, and some parts of Africa. Incidence of prostate cancer is increasing steadily in most countries. Incidence and death rates differ according to race and geographical location. 1 Different autopsy studies performed in Western and Oriental populations have shown that the prevalence of prostate cancer is significantly higher than its incidence. Comparative assessments of these studies have provided similar prevalence rates in different races and geographical areas. 2 The differences in the incidence of prostate cancer in different races and geographical areas and the different progression of this incidence in populations of a race living in a foreign geographical area, strengthen the hypothesis that genetic and lifestyle factors are responsible for the difference in post-induction progression of prostate cancer. 3,4 The incidence rate of clinically apparent prostate cancer is eight-fold higher in the United States than in Japan, while the prevalence of latent prostate cancer, a presumed precursor of clinical prostate cancer, is similar in the two countries. 5 However, the initiating and promoting factors that determine the variability in the natural history of prostate cancer remain unknown. 6 There is a substantial discrepancy between the high incidence of prostate cancer and the extremely low incidence of primary cancer in the seminal vesicles, 7 although the two glands represent neighbouring anatomical locations, both of them being exocrine accessory genital glands and both being under similar hormonal control. Hence, there may be endogenous as well as exogenous factors promotive of prostate cancer development. We hypothesize that prostasomes with their exclusive origin in the prostate gland and with their Received

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

“…The luminal epithelium consists of tall columnar cells that are highly polarized both morphologically and functionally, actively secreting products such as PSA and prostasomes into the glandular lumen. During progress of malignancy, the columnar cells are successively transformed into cuboidal cells that can appear in small conglomerates with loss of polarity, increasingly extending beyond the basal membrane to invade stromal tissue (39). These invasive malignant cells thus are confined to produce and export prostasomes to the interstitial space (27), increasing the probability of uptake in circulating blood.…”

Seminal prostasomes inhibit the angiogenesis activity of rat aortic rings

“…Ronquist and Nilsson suggest that prostasomes may have a wide range of promalignant properties, affecting cell transformation, immunosuppression, proliferation, facilitation of local invasion, and promotion of angiogenesis. 11 Despite this there has been relatively little experimental evidence to either confirm or refute these views, beyond a study demonstrating that semenderived prostasomes exert a growth-inhibitory effect on prostate cancer cells grown in culture. 12 We have previously examined the influence of prostasomes on angiogenesis, demonstrating interaction of prostasomes with endothelial cells and the inhibition of tubule formation by human umbilical vein endothelial cells (HUVEC) grown on matrigel.…”

Extracellular matrix degrading enzymes at the prostasome surface

“…At present, prostate cancer is an enormous medical and socioeconomic problem that is going to worsen because of the aging of the population. 1 Prostasomes are present in human seminal plasma as prostate secretory vesicles, and an ordinary exocytotic event involving the fusion of the membranes that surround the storage vesicle and the prostatic secretory cell is the probable mechanism by which they are released. Discovered more than 20 years ago by Ronquist and Brody, 2 they are now biochemically well characterized.…”

“…These characteristics and the presence of saturated and monounsaturated fatty acids make the prostasome membrane highly ordered and rigid. 1 A proteomic analysis has shown the existence at the prostasome surface of at least 139 proteins including enzymes (35%), transport/structural proteins (19%), GTP proteins(14%), chaperone proteins (6%), signal transduction proteins (17%) and novel proteins (9%). 3 Some of these components have already been shown in the prostasomes.…”

“…3 Some of these components have already been shown in the prostasomes. 1 Dipeptidyl peptidase IV (DPPIV), which has an extremely high specific activity in prostasomes, 4 has been identified as the antigen of a monoclonal antiprostasome antibody, that is, mAb 78. 5 In prostatic cancer tissues, there is an increased activity of DPPIV that may influence the metabolism and encourage cancer growth, 6 and in the highly invasive 1-LN human prostate tumor cell line, DPPIV is connected with the activation of plasminogen and the expression of matrix metalloproteinase (MMP)-9 7 followed by the degradation of extracellular matrix components and cancer invasion.…”