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


METHODS
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.


METHODS
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.


METHODS
In vivo and in vitro evaluation of induction of tumor growth and metastatic potential.


CONCLUSIONS
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.
Thalmann
George N
GN
Department of Urology, University of Bern, Inselspital, 3010 Bern, Switzerland. george.thalmann@insel.ch
Rhee
Hong
H
Sikes
Robert A
RA
Pathak
Sen
S
Multani
Ashi
A
Zhau
Haiyen E
HE
Marshall
Fray F
FF
Chung
Leland W K
LW
D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary; D002277:Carcinoma / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009919:Orchiectomy; D011467:Prostate / Q000254:growth & development / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment
D017430:Prostate-Specific Antigen