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Serum antibodies against prostasomal clusterin in prostate cancer patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. (Prostasomforskning (Anders Larsson))
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Department of Urology-Prostate Centre, University Clinic, Mu¨nster,.
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2008 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 3, 219-227 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Clusterin is a ubiquitous secretory sulphated glycoprotein present in prostasomes. It is an antiapoptotic mediator in prostate cancer and is among the most frequently occurring prostasomal proteins immunogenic in prostate cancer patients. The aim of the present study was to investigate the occurrence of anticlusterin antibodies in the serum of patients with prostate cancer and whether there is a relationship between anticlusterin antibody titres and other clinico-pathological variables. Material and methods. Serum samples were collected from 391 consecutive patients with suspected prostate cancer (150 benign prostate and 241 prostate cancer). The patients’ serum samples were used in an ELISA where microtitre wells were coated with purified clusterin from serum of a healthy volunteer. Flow cytometric studies of clusterin and prostasomes were performed. Results. Flow cytometric analyses revealed the presence of clusterin on the surface of seminal prostasomes. Anti-clusterin ELISA titres in sera of patients did not differ significantly from those of a control group. A significant ‘‘inverse’’ correlation existed between anti-clusterin ELISA titres and lymph node metastases (p50.047), but only 11 out of 161 patients had metastases. These titres correlated significantly with total prostate (p50.021) and transitional zone (p50.015) volumes of the patients. Conclusions. The correlation between serum anti-clusterin antibody titres and other clinico-pathological variables was generally weak in prostate cancer patients, although clusterin has been assigned an important role in tumourigenesis and progression of prostate cancer. However, the anti-clusterin antibody titre appeared to be related to prostate volume, correlating to both transitional zone volume and total volume of the prostate.

Place, publisher, year, edition, pages
2008. Vol. 68, no 3, 219-227 p.
Keyword [en]
Antibodies, clusterin, prostasomes, prostate cancer
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-100731DOI: 10.1080/00365510701604602ISI: 000255454500006PubMedID: 17926197OAI: oai:DiVA.org:uu-100731DiVA: diva2:210990
Available from: 2009-04-07 Created: 2009-04-06 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Some Characteristics of Human Prostasomes and Their Relationship to Prostate Cancer
Open this publication in new window or tab >>Some Characteristics of Human Prostasomes and Their Relationship to Prostate Cancer
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The secretory epithelial cells of the prostate gland use sophisticated vehicles named prostasomes to relay important information to sperm cells in semen. This prostasome-forming and secretory ability of the epithelial cells is also preserved in poorly differentiated prostate cancer cells.

Aim: The aim of this thesis was to examine different characteristics of prostasomes, especially those derived from malignant prostate cells, linked to their potential role in diagnosis and prognostication of prostate cancer.

Results: Serum samples of prostate cancer patients contained autoantibodies against seminal prostasomes in a higher concentration than did control sera. These autoantibodies were most frequently directed against 25 prostasome-associated proteins, but no one was prostate specific. Clusterin was one of the most frequently occurring prostasomal proteins. Elevated titers were however seen in both patients´ and control sera. Clusterin turned out to be a major antigen of seminal prostasomes. No prostate specific or prostate cancer specific protein was discovered upon proteomic analysis of prostasomes deriving from malignant cells of vertebral metastases of prostate cancer patients. Human chromosomal DNA was identified in both seminal prostasomes and PC-3 cell prostasomes and strong evidence existed that the DNA was localized inside the prostasomes. Four out of 13 DNA clones of seminal prostasomes featured gene sequences (31%). The corresponding figures for PC-3 cell prostasomes were 4 out of 16 clones (25%).

Conclusions: Prostasomes are immunogenic and give rise to serum autoantibodies. The most frequently occurring autoantibodies were directed against 25 prostasomal proteins but none of these was exclusively prostate specific. Thirty different proteins were identified in prostate cancer metastasis-derived prostasomes but none of these proteins was prostate cancer specific. Human chromosomal DNA was identified in prostasomes of both normal and malignant cell origin.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 451
Keyword
Prostasomes, prostate, prostate cancer, clusterin, antibodies, metastasis, exosomes, PC-3 cells, DNA vehicles, gene therapy, immunoblotting, mass spectrometry, agarose gel electrophoresis, vertebral metastasis.
National Category
Other Clinical Medicine
Research subject
Clinical Chemistry
Identifiers
urn:nbn:se:uu:diva-100799 (URN)978-91-554-7504-8 (ISBN)
Public defence
2009-05-27, Rosensalen, Akademiska sjukhuset, ing 95, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-05-05 Created: 2009-04-07 Last updated: 2009-05-28Bibliographically approved

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Publisher's full textPubMedhttp://dx.doi.org/10.1080/00365510701604602

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Ronquist, GöranCarlsson, LenaRonquist, GunnarLarsson, Anders

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