title: The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects.
abstract: The side population (SP), recently identified in several normal tissues and in a variety of tumors based on its ability to extrude some fluorescent dyes, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer and found it in 9 of 27 primary tumor samples analyzed, as well as in 4 of 6 cultures from xenotransplants. SP cells from one xenograft bearing a large SP fraction were characterized in detail. SP cells had higher proliferation rates, were much less apoptotic compared with non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of IFN-alpha, a cytokine that has widely been used to treat solid tumors, on epithelial ovarian cancer cells and observed that IFN-alpha exerted marked antiproliferative and proapoptotic effects on primary cultures containing high numbers of SP cells. In vitro, IFN-alpha treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origins; moreover, IFN-alpha treatment of purified SP cells was associated with a distinctive change in their 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 because they imply that tumors bearing large SP numbers, albeit rare, could be sensitive to IFN-alpha treatment.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Moserle
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Margherita
authors.initials: M
authors.lastname: Ghisi
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.forename: Elena
authors.initials: E
authors.lastname: Fortunato
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Silvia
authors.initials: S
authors.lastname: Miotti
authors.forename: Valeria
authors.initials: V
authors.lastname: Tosello
authors.forename: Rita
authors.initials: R
authors.lastname: Zamarchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Corradin
authors.forename: Sonia
authors.initials: S
authors.lastname: Minuzzo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha