| Prostate cancer is the second leading cause of death from cancer in American men. Using a family of human prostate cancer cell lines developed in our laboratory, that mimic multiple steps in tumor progression, I developed xenograft models using the RWPE2-W99, WPE1-NB26, and CTPE cell lines. When injected sub-cutaneously into immune-deficient mice, RWPE2-W99 forms slow growing, WPE1-NB26 rapidly growing, and CTPE more aggressive, metastatic tumors. I derived two new cell lines, WPE1-NB26-64 and WPE1-NB26-65, from WPE1-NB26 tumors which show increased growth as compared to the parent WPEI-NB26 cells. Cells express cytokeratin 18, androgen receptor and prostate-specific antigen, establishing their prostatic epithelial origin. WPEI-NB26-65 is more invasive than WPE1-NB26 which, in part, may be associated with increased expression of matrix metalloproteinases, MMP-2 and MMP-9, which are barely detectable in WPE1-NB26 cells. Results also show that chemically modified tetracyclines, potential new drugs for cancer treatment, CMTs 2147 and 2215, inhibited cancer cell growth in vitro and reduced the size and number of RWPE2-W99 tumors in vivo, which mimic the behavior of the majority of human prostate cancers. These results have important applications in studies on tumor progression and for evaluating the efficacy of new drugs for the treatment of prostate cancer. |
