Human prostate fibroblasts induce growth and confer castration resistance and metastatic potential in LNCaP Cells.

Autor: Thalmann GN; Department of Urology, University of Bern, Inselspital, 3010 Bern, Switzerland. george.thalmann@insel.ch, Rhee H, Sikes RA, Pathak S, Multani A, Zhau HE, Marshall FF, Chung LW
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2010 Jul; Vol. 58 (1), pp. 162-71. Date of Electronic Publication: 2009 Sep 04.
DOI: 10.1016/j.eururo.2009.08.026
Abstrakt: Background: The tumor microenvironment is important for progressive and metastatic disease.
Objective: To study the hypothesis that prostate fibroblasts have differential ability to induce castration-resistant prostate cancer (PCa) and metastatic progression and whether this effect might vary depending on the zonal origin of the fibroblast.
Design, Setting, and Participants: Human prostate fibroblasts from the peripheral (PZ), transition (TZ) and central (CZ) zones of radical prostatectomy specimens (n=13) were isolated and compared for their ability to promote androgen independence and metastatic progression in androgen-responsive PCa lymph node carcinoma of the prostate (LNCaP) cells in vivo.
Interventions: By coinoculating marginally tumorigenic LNCaP cells with PZ or TZ and by altering host hormonal milieu, a series of tumorigenic and metastatic LNCaP epithelial sublines-P4, P4-2 (derivatives from interaction with PZ), T4, and T4-2 (derivatives from interaction with TZ)-were established and characterized.
Measurements: In vivo and in vitro evaluation of induction of tumor growth and metastatic potential.
Results and Limitations: 1) LNCaP sublines were permanently altered in their cytogenetic and biologic profiles after cellular interaction with prostate stromal fibroblasts. LNCaP sublines grew faster under anchorage-dependent and -independent conditions, expressed 1-12-fold more prostate-specific antigen in vitro than LNCaP cells, and gained metastatic potential; 2) zonal differences of stromal fibroblasts in their ability to induce the growth and progression of LNCaP tumors as xenografts in mice may exist but need further analysis; 3) PZ-conditioned medium induced more anchorage-independent growth of LNCaP cells in vitro. TZ had a higher growth rate and were more sensitive to dihydrotestosterone.
Conclusions: We demonstrate that prostate fibroblasts have growth inductive potential on PCa cells and affect their subsequent progression to castration resistance and development of a metastatic phenotype.
(Copyright 2009 European Association of Urology. All rights reserved.)
Databáze: MEDLINE
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