Monoclonal antibodies against human prostasomes

Nilsson, Bo; Jin, Meishan; Einarsson, Barbro; Persson, Bo‐Eric; Ronquist, Gunnar

doi:10.1002/(sici)1097-0045(19980515)35:3<178::aid-pros3>3.0.co;2-d

Cited by 36 publications

(25 citation statements)

References 39 publications

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“…Monoclonal antibodies mAb78 and mAb8H10, directed against seminal prostasomes, were produced in mice by intrasplenic immunization, and the antibodies were biotinylated as described (17,47,48). The mAb78 was previously used to recognize prostasomes in benign and neoplastic cells of the prostate gland (26,47) and PC-3 cells (25), indicative of its functionality in a cell-biological context.…”

Section: Methodsmentioning

confidence: 99%

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

Tavoosidana

Ronquist

Darmanis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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201

173

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Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

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Section: Methodsmentioning

confidence: 99%

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

Tavoosidana

Ronquist

Darmanis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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201

173

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“…18 However, a monoclonal antibody raised against purified prostasomes not only recognised prostasomes but also antigen epitopes from some other cells, for example, exocrine/ endocrine pancreatic cells, monocytes/macrophages and seminal vesicle epithelial cells. 10 Hence, present immunomarkers for prostasomes demonstrate varying degrees of crossreactivity to other cells, which means that such studies alone are not enough to constitute the basis for establishment of the organ origin of prostasomes in semen.…”

Section: Prostasomes and Their Organ Originmentioning

confidence: 99%

“…There is strong evidence that prostasomes are unique structures derived only from the prostate gland in man. 9,10 This statement is based on the following lines of evidence.…”

Section: Prostasomes and Their Organ Originmentioning

confidence: 99%

“…125 It should, however, be pointed out that coordinated breakdown, synthesis and remodelling of the extracellular matrix are crucial events in normal physiological situations, such as embryonic development, reproduction, wound healing and angiogenesis. 126 No studies have so far been carried out to investigate whether MMPs are associated with prostasomes which occur not only in normal prostate epithelial cells 10 but also in malignant prostate epithelial cells. 109 …”

Section: Malignant Conversion Activitymentioning

confidence: 99%

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

Ronquist

Nilsson

2004

Prostate Cancer Prostatic Dis

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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

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“…Prostasomes are a granular type of secretory product in the prostate gland cells (2, 10) Immunostaining of the prostate epithelium with anti-prostasome antibodies displays a secretion, which is assumed to be related to the prostasomes (7,8). When the normal prostate epithelium passes a neoplastic transformation, the secretory activity of the cells decreases and at high Gleason grades, the immunostained secretion disappears (6).…”

Section: Introductionmentioning

confidence: 99%

Expression of Prostasome-like Granules by the Prostate Cancer Cell Lines PC3, Dul45 and LnCaP Grown in Monolayer

Nilsson¹,

Lennartsson²,

Carlsson³

et al. 1999

Upsala Journal of Medical Sciences

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Prostasomes are a granular type of secretory product in the human prostate gland cells. It is not known, whether in vitro grown cells derived from human prostate cancers also express prostate secretory components containing granules with properties similar to the prostasomes. Therefore, we carried out the present investigation and found that cytospins of in vifro grown PC3, DU14S and LNCaP cells generally expressed a granular secretion. DU145 demonstrated the highest ratio of cells with granules (about 90%), while cytospins of PC3 and LNCaP contained less stained cells (50-70%). Purified granules from PC3 cells were immunoreactive with a monoclonal antibody (mAb78) originally raised against human seminal prostasomes. The PC3 granules also shared the property with human seminal prostasomes having an elevated UV260/UV280 absorbance ratio. On the other hand we found a low aminopeptidase activity in PC3 granules contrary to that of human prostasomes. Prostasomes may form a heterogeneous group with different properties due to the source from which they are isolated and perhaps it is justified to recognize them as different members of a prostasome family.

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Monoclonal antibodies against human prostasomes

Cited by 36 publications

References 39 publications

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

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

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

Expression of Prostasome-like Granules by the Prostate Cancer Cell Lines PC3, Dul45 and LnCaP Grown in Monolayer

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