Transcription profiling of human side population ovarian cancer cells treated with IFN-alfa

ABSTRACT: The side population (SP), recently identified in several normal tissues and in a variety of tumors, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer (EOC) and found it in 4 out of 6 primary cultures from xenotransplants, as well as in 9 out of 25 clinical samples analyzed. SP cells from one xenograft bearing a large SP fraction were characterized in detail and they were capable of recreate the full repertoire of cancer cell populations observed in the parent tumor. Moreover, SP cells had higher proliferation rates, were much less apoptotic compared to non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of interferon-alfa (IFN-alpha), a cytokine which has been widely used to treat solid tumors, on EOC cells and observed that IFN-alpha exerts marked anti-proliferative and pro-apoptotic effects on primary cultures containing SP cells. IFN-alfa-treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origin and in normal bone-marrow SP cells, associated with a distinctive transcriptional profile. Gene therapy with human IFN-alpha resulted in regression of established tumors bearing a large SP fraction, which was not observed when tumors bearing low SP levels were treated. These findings could have relevant clinical implications since they imply that tumors bearing large SP numbers - albeit rare - could be sensitive to IFN-alpha treatment. Experiment Overall Design: 4 Affymetrix microarrays: Experiment Overall Design: 2 technical replicates: Ovarian cancer, untreated Side Population, rep1 Experiment Overall Design: Ovarian cancer, untreated Side Population, rep2 Experiment Overall Design: + Experiment Overall Design: 2 technical replicates: Ovarian cancer, IFN-alpha treated Side Population, rep1 Experiment Overall Design: Ovarian cancer, IFN-alpha treated Side Population, rep2

ORGANISM(S): Homo sapiens

SUBMITTER: Alberto Corradin 

PROVIDER: E-GEOD-9481 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress