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Proteomic analysis of prostate cancer metastasis: derived prostasomes
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
2010 (English)In: Anticancer Research, ISSN 0250-7005, Vol. 30, no 2, 285-290 p.Article in journal (Refereed) Published
Abstract [en]

The secretory epithelial cells of the prostate gland use sophisticated vehicles in the form of 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. We investigated prostasomes from vertebral metastases of prostate cancer, taken from the operating field at surgery, directly taken care of under protease inhibitory conditions for later 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) protein characterization. A total of 104 spots were punched out for identification. Twenty five unique protein spots had a MALDI-TOF above 49 and another 5 proteins were determined by MS/MS. The remaining 74 spots were either identical to already determined proteins or had no reliable score. Annexins A1, A3, and A5 as well as dimethylarginine dimethylaminohydrolase 1 were among the identified proteins. The annexins and dimethylarginine dimethylaminohydrolase 1 found in cancer-derived prostasomes can act, among other things, as angiogenic factors and can increase the vascular development in the neighborhood of the tumor. Cancer-derived prostasomes may play an important role in the interaction between tumor cells and their environment.

Place, publisher, year, edition, pages
2010. Vol. 30, no 2, 285-290 p.
Keyword [en]
Metastasis, prostasomes, exosomes, annexin
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-100733ISI: 000275821200002PubMedID: 20332430OAI: oai:DiVA.org:uu-100733DiVA: diva2:210996
Available from: 2009-04-07 Created: 2009-04-06 Last updated: 2010-12-14Bibliographically 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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