Proper Migration Of Mammalian Prostate Stem Cells To The Area Of The Prostate Gland In Zebrafish

Androgen independent prostate cancer contributes to the maximum mortality in prostate cancer patients. One school of thought is that these cancer cells arise in metastatic sites where the cancer cells take on stem cell behavior similar to the stem cell behavior observed in normal prostate gland. Thus, understanding prostate gland stem cells and their migration pattern may provide clues to their biology which may have applications in their migration during metastasis. To understand the migration of mammalian prostate stem cells we used zebrafish as a model. We have previously established zebrafish as a model to study prostate cancer because we found the presence of prostate-like- cells around the zebrafish testes. In this abstract we further characterized location of normal prostate-like cells. We found that they are present in the anterior and posterior aspects of testes. Furthermore, we cloned 2 kb prostate specific antigen promoter into pDsRed 2.1 plasmid and injected this plasmid DNA into single cell-stage zebrafish embryo with I-Sce1 to enhance transgenesis frequency and germline transmission. Larvae injected with PSA promoter-DSRed 2 constructs were screened three days post fertilization (dpf) for the expression of red fluorescence, which was observed in bilaterally arranged spots in gonads. We then used 5 dpf zebrafish larvae and IV-injected cells from four different cell lines expressing either GFP or RFP: two with stem cell phenotype RWPE-1-shDAB2IP (GFP), PZ-HPV7-shDAB2IP (GFP), and two as controls RWPE-1-shCon (GFP) and PC-3 (RFP). After two days, microscopy for green or red fluorescence signal revealed RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells bilaterally migrated to the yolk, i.e. the similar area where PSA promoter expression was found. This specific migration was not observed with RWPE-1-shCon and PC-3 cells lines. These same fluorescence reporter experiments were performed in parallel in 48 hr and 72 hr post fertilization (hpf) dechorinated larvae. We observed similar results in the 72 hpf larvae as were found in 5 dpf larvae but not in the 48 hpf larvae. Taken together, these results suggest that RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells have the homing receptors necessary for migrating to the same area in gonads. Understanding these homing mechanisms may be relevant for controlling the abnormal migration in metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4377. doi:10.1158/1538-7445.AM2011-4377