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Eur Urol. 2010 Jul;58(1):162-71. doi: 10.1016/j.eururo.2009.08.026. Epub 2009 Sep 4.

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

Author information

1
Department of Urology, University of Bern, Inselspital, 3010 Bern, Switzerland. george.thalmann@insel.ch

Abstract

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.

PMID:
19747763
PMCID:
PMC2889152
DOI:
10.1016/j.eururo.2009.08.026
[Indexed for MEDLINE]
Free PMC Article

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