CL1-GFP: An androgen independent metastatic tumor model for prostate cancer

Purpose: The mechanisms responsible for tumor progression to androgen indep endence in prostate cancer (CaP) remain unknown. To characterize these chan ges and provide a basis for rational therapeutic strategies for advanced Ca P, an in vivo model from a highly aggressive androgen independent CaP cell line with distinct cellular and molecular properties was developed. Materials and Methods: An aggressive androgen-independent cell line designa ted CL1 was derived from a slow-growing, and androgen-dependent, parental L NCaP cell line through in-vitro androgen-deprivation and selection. CL1 was stably transfected with a green fluorescence protein gene (CL1-GFP) and or thotopically injected into SCID mice. The pathologic behavior, histology, a nd molecular determinants of CL1 tumor and metastases were determined and c haracterized by standard light and fluorescent microscopy, and quantitative RT-PCR analysis. Results: CL1 is an anaplastic prostate cancer cell line which demonstrates extensive local invasion and metastases to various organs that can be visua lized via GFP expression. When compared with parental LNCaP cells, RT-PCR a nalysis of the tumor revealed an over-expression of EGFR, b-FGF, VEGF, TGF- beta, IL-8, IL-6, and bcl-2 and a down regulated expression of the p53, E-c adherin and PTEN. In contrast to LNCaP cells, CL1 tumors express lower leve ls of androgen receptor and barely detectable PSA mRNA. Conclusions: CL1-GFP represents an aggressive androgen-independent CaP tumo r model derived through androgen deprivation whose pathologic development a nd molecular properties in animals resembles the clinical characteristics o f hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP ca n be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modaliti es.