CYSTATIN C AND NEUROENDOCRINE DIFFERENTIATION IN THE MALE REPRODUCTIVE SYSTEM AND IN PROSTATE CANCER

Thomas Jiborn

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Cystatins are endogenous protease inhibitors that regulate the proteolytic activities of family C1 (papain-like) cysteine proteases, such as human cathepsins B, H, K, L, and S. Cystatin C shows the fastest inhibition and the highest affinity of all cystatins towards lysosomal cysteine proteases in general and is widespread in human tissues and body fluids. Alterations in the balance between the cysteine proteases and the cystatins have been associated with cancer cell invasion and metastasis.

Neuroendocrine cells, containing growth stimulatory hormones, are found in various degrees in the vast majority of prostatic adenocarcinomas, and neuroendocrine differentiation has been correlated with tumor progression and resistance to hormonal therapy. Recent immunohistochemical studies suggest that there may be a relationship between cystatin C and the neuroendocrine system. The aim of this thesis was to examine cystatin C and neuroendocrine differentiation in the male genital tract and in prostate cancer.

RESULTS AND CONCLUSIONS:

1. Cystatin C is highly expressed and widely distributed in benign tissues throughout the male genital tract, indicating that cystatin C is an important local protease inhibitor in these tissues.

2. Cystatin C is produced by prostate cancer cells in vivo and in vitro.

3. The expression of cystatin C is altered in prostate cancer relative to that in benign prostatic tissues, and there is an association between increased cathepsin B / cystatin C ratio and cancer progression and advanced disease.

4. The number of prostatic neuroendocrine cells increases during hormonal treatment, indicating that androgen-deprivation therapy enhances the selection and progression of androgen-independent neuroendocrine tumor cells.

5. Our finding of scattered, strongly cystatin C-positive neuroendocrine-like cells in prostate cancer tissues suggests that cystatin C may be a useful tissue marker for neuroendocrine differentiation in prostate cancer.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Clinical Sciences, Malmö
Supervisors/Advisors
  • Bjartell, Anders, Supervisor
Award date2006 Nov 3
Publisher
Print ISBNs91-85559-39-3
Publication statusPublished - 2006

Bibliographical note

Defence details

Date: 2006-11-03
Time: 09:15
Place: Jubileumsaulan, Medicinskt forskningscentrum, ingång 59, Universitetssjukhuset MAS Malmö

External reviewer(s)

Name: Brünner, Nils
Title: Professor
Affiliation: Royal Veterinary and Agriculture University, DK-1870 Frederiksberg C, Danmark

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<div class="article_info">T Jiborn, M Abrahamson, H Wallin, J Malm, Å Lundwall, V Gadaleanu, P-A Abrahamsson and A Bjartell. <span class="article_issue_date">2004</span>. <span class="article_title">Cystatin C is highly expressed in the human male reproductive system.</span> <span class="journal_series_title">J Androl</span>, <span class="journal_volume">vol 25</span> <span class="journal_pages">pp 564-572</span>.</div>
<div class="article_info">T Jiborn, M Abrahamson, V Gadaleanu, Å Lundwall and A Bjartell. <span class="article_issue_date">2006</span>. <span class="article_title">Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation.</span> <span class="journal_series_title">BJU Int</span>, <span class="journal_volume">vol 98</span> <span class="journal_pages">pp 189-196</span>.</div>
<div class="article_info">T Jiborn, A Bjartell and P-A Abrahamsson. <span class="article_issue_date">1998</span>. <span class="article_title">Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment.</span> <span class="journal_series_title">Urology</span>, <span class="journal_volume">vol 51</span> <span class="journal_pages">pp 585-589</span>.</div>
<div class="article_info">T Jiborn, M Abrahamson, V Gadaleanu, WL Gerald, JM Satagopan and A Bjartell. <span class="article_issue_date"></span>. <span class="article_title">Increased cathepsin B/cystatin C ratio in prostate cancer is associated with advanced tumor stage and disease progression during hormonal treatment.</span> (manuscript)</div>
<div class="article_info">T Jiborn, M Abrahamson and A Bjartell. <span class="article_issue_date"></span>. <span class="article_title">Cystatin C is produced and secreted by three human prostate cancer cell lines.</span> (manuscript)</div>


The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Urology (013243400), Division of Urological Cancers (013243420)

Subject classification (UKÄ)

  • Urology and Nephrology

Keywords

  • Urology
  • androgen deprivation therapy
  • cysteine protease inhibitor
  • neuroendocrine differentiation
  • cysteine protease
  • male reproductive tract
  • prostate cancer
  • nefrologi
  • Urologi
  • nephrology

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