title: Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells.
abstract: Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer.
authors.affiliation: Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Eriksson
authors.forename: Kilian
authors.initials: K
authors.lastname: Guse
authors.forename: Gerd
authors.initials: G
authors.lastname: Bauerschmitz
authors.forename: Pekka
authors.initials: P
authors.lastname: Virkkunen
authors.forename: Maija
authors.initials: M
authors.lastname: Tarkkanen
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.forename: Tanja
authors.initials: T
authors.lastname: Hakkarainen
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Renee A
authors.initials: RA
authors.lastname: Desmond
authors.forename: Sari
authors.initials: S
authors.lastname: Pesonen
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D051927:CD24 Antigen / Q000276:immunology*; D017931:DNA Primers; D018960:Hyaluronan Receptors / Q000276:immunology*; D051379:Mice
chemical_list: D051927:CD24 Antigen; D017931:DNA Primers; D018960:Hyaluronan Receptors