Targeting STAMP1 for prostate cancer progression and metastasis
Our laboratory is studying proteins that are implicated in the progression of prostate cancer (PCa) and have previously identified a number of genes that are involved in this regard. One of these is the Six-transmembrane protein 1 (STAMP1), a prostate enriched protein. In vitro and in vivo studies showed that knockdown of STAMP1 resulted in significant growth suppression of PCa cells LNCaP, VCaP and 22Rv1, representing both androgen dependent and castration resistance stages of PCa. This suggests that STAMP1 is crucial for the growth of PCa cells and represent a potentially promising new therapeutic target. The current application have two major goals: a. to investigate the potential function of STAMP1 in PCa cell metastasis in vivo; b. to assess the therapeutic efficacy of targeting STAMP1 using nanoliposome mediated delivery technique, in treating PCa tumor growth and metastasis in preclinical xenograft mouse model. To this end, cell lines expressing luciferase intravenously injected into nude mice to allow for the development of distant metastases and in vivo imaging. PCa cells will also be engrafted subcutaneously into the flanks of nude mice, which will be treated with nanoliposomal siRNA against STAMP1 to determine the efficacy of targeting STAMP1 in treating PCa tumor growth.
Regarding the 3R, in vitro experiments have already been performed. To investigate whether the results obtained in vitro are applicable to an in vivo setting, experiments in live animals are necessary. Eight animals per group should give sufficient data to obtain statistical significance of the results based on our/others experience in similar experiments. Smaller groups of animals may not give enough statistical power. The cell lines used will be tested for contaminating microorganisms and infectious agents such as mycoplasma and hepatitis. The animals will be anesthetized using isofluran prior to intravenous cell injection to prevent discomfort to the animals.
Regarding the 3R, in vitro experiments have already been performed. To investigate whether the results obtained in vitro are applicable to an in vivo setting, experiments in live animals are necessary. Eight animals per group should give sufficient data to obtain statistical significance of the results based on our/others experience in similar experiments. Smaller groups of animals may not give enough statistical power. The cell lines used will be tested for contaminating microorganisms and infectious agents such as mycoplasma and hepatitis. The animals will be anesthetized using isofluran prior to intravenous cell injection to prevent discomfort to the animals.