uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Prostasome-derived proteins capable of eliciting an immune response in prostate cancer patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. (Biokemisk struktur och funktion)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. (Biokemisk struktur och funktion)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. (Biokemisk struktur och funktion)
Karolinska University Hospital, Department of Oncology and Pathology.
Show others and affiliations
2006 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 4, 847-853 p.Article in journal (Refereed) Published
Abstract [en]

Prostate cancer consistently remains a difficult clinical enigma. Therefore, the development of novel strategies for diagnosis and treatment (e.g. immunotherapy) of prostate cancer is essential. We tried to identify the prostasome-derived proteins that were immunogenic in prostate cancer patients. Prostate cancer patients’ sera (n 5 44) with high enzyme-linked immunosorbent assay (ELISA) titers against prostasomes were selected for immunoblotting against purified seminal prostasomes. The SDS-PAGE and immunoblotting experiments were performed with Bio-Rad systems. Twenty-five of the recognized proteins were isolated and analyzed by means of mass spectrometry. Out of 44 patients’ sera, 31 (70%) demonstrated in immunoblotting experiments reactivity against several prostasomal protein bands in the molecular weight range of 10– 200 kDa. Some of the bands (55, 70 and 170 kDa) were more frequently recognized by the patients’ sera. Concomitantly run control sera generated only very weak or no bands at all. The most frequently occurring prostasomal proteins were identified as heat shock proteins (HSP 70, 71) and clusterin. This study identified the most important molecular targets of autoantibodies against prostasomes generated in connection with the development of prostate cancer in man. These immunogenic prostasomal proteins could be appropriate target molecules for specific immunotherapy of prostate cancer patients.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Place, publisher, year, edition, pages
2006. Vol. 119, no 4, 847-853 p.
Keyword [en]
prostate, prostasomes, prostate cancer, immunoblotting
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-100724DOI: 10.1002/ijc.21895PubMedID: 16557587OAI: oai:DiVA.org:uu-100724DiVA: diva2:210993
Available from: 2009-04-07 Created: 2009-04-06 Last updated: 2010-05-27Bibliographically 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

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedwww.interscience.wiley.com

Authority records BETA

Ronquist, GöranCarlsson, LenaRonquist, GunnarLarsson, Anders

Search in DiVA

By author/editor
Ronquist, GöranCarlsson, LenaRonquist, GunnarLarsson, Anders
By organisation
Clinical Chemistry
In the same journal
International Journal of Cancer
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 473 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf