Derivation of Androgen-Independent LNCaP Sublines from Cell-Cell Interactions of LNCaP and Human Prostate Fibroblasts in vivo.
- Author:
Hong Woo RHEE
1
;
Leland W K CHUNG
Author Information
1. Department of urology, Catholic University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Cell-cell interaction;
LNCaP;
Prostate fibroblast;
Androgen-independent
- MeSH:
Animals;
Cytogenetics;
Epithelium;
Fibroblasts*;
Humans*;
Liver;
Lung;
Lymph Nodes;
Mice;
Mice, Nude;
Parents;
Prostate*;
Prostatic Neoplasms
- From:Korean Journal of Urology
1999;40(11):1478-1486
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: A cell-cell interaction in which in vivo inoculation of androgen-dependent, non-tumorigenic LNCaP and human bone fibroblast resulted in derivation of androgen-independent and metastatic LNCaP subline(C4-2) in castrated hosts. The purpose of this study is to evaluate if human prostate fibroblasts when grown together with LNCaP may promote androgen-independent growth and enhance metastatic potential. MATERIALS AND METHODS: LNCaP cells and human prostate fibroblasts derived either from peripheral or transition zone co-inoculated in athymic mice for 8 weeks, and then mice were castrated. The chimeric tumors were maintained for additional 4 weeks. The LNCaP sublines, designated P4 and T4, were established and characterized. These sublines were co-inoculated again in castrated mice with human prostate fibroblasts for 8-12 weeks. And then second generation LNCaP sublines, P4-2 and T4-2, were established and also characterized. RESULTS: Marked cytogenetic alterations were observed in P4-2, P4, T4-2 and T4 LNCaP sublines in comparison to parental LNCaP. Although LNCaP cells injected orthotopically did not form tumors in castrated hosts, LNCaP sublines formed PSA-producing tumors and had metastatic potentials to lymph node, lung, liver and bone. These P and T sublines had androgen-independent growth characteristics and metastatic potential. CONCLUSIONS: Cell-cell interactions between prostatic epithelium and their surrounding fibroblasts could contribute to androgen-independent characteristics and enhanced metastatic potential of localized prostate cancer in vivo.
