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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Malignant transformation in a nontumorigenic human prostatic epithelial cell line
1Department of Urology, University of California-San Francisco, San Francisco, CA 94143, USA. simon.hayward@mcmail.vanderbilt.edu
Cancer Research
|November 24, 2001
Summary
The BPH-1 prostate cell line can become tumorigenic when exposed to specific microenvironments, such as carcinoma-associated fibroblasts or hormones. These transformed cells, when studied, offer insights into the mechanisms of prostate cancer development.
Area of Science:
- Urology
- Cancer Biology
- Cell Biology
Background:
- The BPH-1 human prostatic epithelial cell line is typically non-tumorigenic in immunocompromised mouse models.
- Understanding the factors that induce tumorigenicity in epithelial cells is crucial for advancing prostate cancer research.
Purpose of the Study:
- To investigate the microenvironmental factors that can induce permanent tumorigenicity in the BPH-1 cell line.
- To establish and characterize new tumorigenic sublines derived from BPH-1 cells for further study of carcinogenesis.
Main Methods:
- BPH-1 cells were exposed to either human carcinoma-associated fibroblasts (CAFs) or carcinogenic doses of testosterone and estradiol (T+E2) in combination with rat urogenital sinus mesenchyme.
- Tumorigenic epithelial cells were isolated, cultured as cell strains, and re-grafted into nude mice to assess sustained tumorigenicity.
- Characterization of the derived cell strains included in vitro assays (soft agar colony formation) and in vivo tumor formation, along with immunocytochemical analysis of specific markers (cytokeratins, p63, vimentin, E-cadherin, SV40 large T antigen, and hormone receptors).
Main Results:
- Both CAF and T+E2 treatments induced tumorigenic BPH-1 sublines (BPH1(CAFTD) and BPH1(TETD)), which remained tumorigenic even after removal of the inducing agents.
- BPH1(CAFTD) strains formed colonies in soft agar, unlike parental BPH-1 or BPH1(TETD) cells, indicating distinct transformation characteristics.
- All derived tumor strains consistently formed poorly to moderately differentiated squamous or adenosquamous tumors in vivo, expressing basal and luminal cytokeratins, p63, and SV40 large T antigen, but lacked detectable AR, ERalpha, or PR.
Conclusions:
- The microenvironment plays a critical role in the malignant transformation of prostatic epithelial cells.
- The established BPH-1 derived tumorigenic cell strains are valuable tools for studying the genetic and phenotypic alterations during prostate carcinogenesis.
- These cell strains provide a model for investigating the transition from a non-tumorigenic to a tumorigenic state in prostate cancer.
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