Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways

By Marra, Emanuele; Uva, Paolo; Viti, Valentina; Simonelli, Valeria; Dogliotti, Eugenia; De Rinaldis, Emanuele; Lahm, Armin; La Monica, Nicola; Nicosia, Alfredo; Ciliberto, Gennaro; et al
From BMC Cancer (2010), 10, 129. Language: English, Database: CAPLUS, DOI:10.1186/1471-2407-10-129

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochem. and mRNA anal. It has been targeted by monoclonal antibodies in preclin. animal models and more recently in a clin. trial in prostate cancer patients. The biol. role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth. Methods: A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biol. role in tumor growth, microarray anal. was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR. Results: Down regulation of the PSCA expression was assocd. with reduced cell proliferation in vitro and in vivo. Mice bearing s.c. tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway anal. of deregulated genes suggests a statistical significant assocn. between PSCA downregulation and activation of genes downstream of the IFN α/β receptor. Conclusions: These expts. established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.