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

Jiborn, Thomas LU (2006)
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... (More)
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. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Cystatiner är endogena proteasinhibitorer som reglerar den proteolytiska aktiviteten hos papainlika cysteinproteaser, så som humant cathepsin B, H, K, L och S. Cystatin C, som finns i de flesta humana vävnader och vävnadsvätskor, är den starkaste hämmaren av lysosomala cysteinproteaser. Förändring i balansen mellan cysteinproteaser och cystatiner har vid flera olika cancersjukdomar visat sig vara associerad med invasiv förmåga och metastasering.



Neuroendokrina celler, vilka innehåller tillväxtbefrämjande peptidhormoner, detekteras i varierande grad i en majoritet av alla prostatacancrar, och man har funnit en korrelation mellan neuroendokrin differentiering och hormonoberoende... (More)
Popular Abstract in Swedish

Cystatiner är endogena proteasinhibitorer som reglerar den proteolytiska aktiviteten hos papainlika cysteinproteaser, så som humant cathepsin B, H, K, L och S. Cystatin C, som finns i de flesta humana vävnader och vävnadsvätskor, är den starkaste hämmaren av lysosomala cysteinproteaser. Förändring i balansen mellan cysteinproteaser och cystatiner har vid flera olika cancersjukdomar visat sig vara associerad med invasiv förmåga och metastasering.



Neuroendokrina celler, vilka innehåller tillväxtbefrämjande peptidhormoner, detekteras i varierande grad i en majoritet av alla prostatacancrar, och man har funnit en korrelation mellan neuroendokrin differentiering och hormonoberoende tumörprogress. Resultaten av nyligen publicerade immunohistokemiska studier talar för att det kan finnas en koppling mellan cystatin C och det neuroendokrina systemet. Syftet med denna avhandling har varit att studera cystatin C och neuroendokrin differentiering i det manliga reproduktionssystemet och i prostatacancer.



RESULTAT OCH KONKLUSION:



1. Cystatin C uttrycks i hög grad, såväl på mRNA nivå som på proteinnivå, i benign vävnad i hela det manliga reproduktionssystemet (testikel, bitestikel, sädesledare, sädesblåsor och prostata). Våra resultat talar för att cystatin C är en viktig lokal hämmare av cysteinproteaser i dessa organ.



2. Cystatin C produceras i prostatacancerceller in vivo och in vitro.



3. Uttrycket av cystatin C är förändrat i prostatacancer jämfört med benign prostatavävnad, och en ökad cathepsin B / cystatin C kvot är associerat med cancerprogress och avancerade tumörstadier.



4. Antalet neuroendokrina tumörceller ökar i prostatacancer under hormonell behandling, vilket talar för att hormonell behandling förstärker selektionen och tillväxten av hormonoberoende neuroendokrina tumörceller.



5. Cystatin C uppvisar två olika immunohistokemiska infärgningsmönster i benign och malign prostatavävnad. Utöver en generell, granulerad infärgning i basalceller och sekretoriska celler, har vi också funnit spridda, starkt cystatin C-positiva, neuroendokrin-liknande celler. Våra resultat talar för att cystatin C kan vara en ny vävnadsmarkör för neuroendokrin differentiering vid prostatacancer. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Brünner, Nils, Royal Veterinary and Agriculture University, DK-1870 Frederiksberg C, Danmark
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Urology, androgen deprivation therapy, cysteine protease inhibitor, neuroendocrine differentiation, cysteine protease, male reproductive tract, prostate cancer, nefrologi, Urologi, nephrology
pages
140 pages
publisher
Department of Urology, Malmö University Hospital, 205 02 Malmö, Sweden
defense location
Jubileumsaulan, Medicinskt forskningscentrum, ingång 59, Universitetssjukhuset MAS Malmö
defense date
2006-11-03 09:15:00
ISBN
91-85559-39-3
language
English
LU publication?
yes
additional info
T Jiborn, M Abrahamson, H Wallin, J Malm, Å Lundwall, V Gadaleanu, P-A Abrahamsson and A Bjartell. 2004. Cystatin C is highly expressed in the human male reproductive system. J Androl, vol 25 pp 564-572.
T Jiborn, M Abrahamson, V Gadaleanu, Å Lundwall and A Bjartell. 2006. Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation. BJU Int, vol 98 pp 189-196.
T Jiborn, A Bjartell and P-A Abrahamsson. 1998. Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology, vol 51 pp 585-589.
T Jiborn, M Abrahamson, V Gadaleanu, WL Gerald, JM Satagopan and A Bjartell. . Increased cathepsin B/cystatin C ratio in prostate cancer is associated with advanced tumor stage and disease progression during hormonal treatment. (manuscript)
T Jiborn, M Abrahamson and A Bjartell. . Cystatin C is produced and secreted by three human prostate cancer cell lines. (manuscript)
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)
id
7c95a3cd-4418-42c1-8744-e4997d99e219 (old id 547396)
date added to LUP
2016-04-01 15:46:36
date last changed
2018-11-21 20:36:16
@phdthesis{7c95a3cd-4418-42c1-8744-e4997d99e219,
  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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
RESULTS AND CONCLUSIONS:<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
2. Cystatin C is produced by prostate cancer cells in vivo and in vitro.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.}},
  author       = {{Jiborn, Thomas}},
  isbn         = {{91-85559-39-3}},
  keywords     = {{Urology; androgen deprivation therapy; cysteine protease inhibitor; neuroendocrine differentiation; cysteine protease; male reproductive tract; prostate cancer; nefrologi; Urologi; nephrology}},
  language     = {{eng}},
  publisher    = {{Department of Urology, Malmö University Hospital, 205 02 Malmö, Sweden}},
  school       = {{Lund University}},
  title        = {{CYSTATIN C AND NEUROENDOCRINE DIFFERENTIATION IN THE MALE REPRODUCTIVE SYSTEM AND IN PROSTATE CANCER}},
  year         = {{2006}},
}