title: The CD49d+/high subpopulation from isolated human breast sarcoma spheres             possesses tumor-initiating ability.
abstract: Primary breast sarcomas (PBSs) that arise from mammary stroma are very rare,             highly aggressive and therapy- resistant tumors with a heterogeneous phenotype.             In this study, we sought to identify tumor-initiating cells (TICs) in PBSs and             to describe their features. We isolated long-term self-renewing sarcospheres (designated             NDY-1) from primary breast carcinosarcoma tissue (sarcoma component >95%) using             the anchorage-independent culture method. NDY-1 spheres expressed various mesenchymal             cell markers, and their tumorigenic potential was markedly reduced in adherent             culture conditions, compared to spheres. Screening for integrins revealed a marked             decrease in CD49d expression in adherent culture conditions of NDY-1. The CD49d+/high             subpopulation sorted from NDY-1 spheres displayed higher cell viability and sphere-forming             ability than CD49d-/low population in vitro. Moreover, the CD49d+/high population             displayed high tumor initiating ability in limiting dilution transplantation to             NOD/SCID mice, and the xenotransplanted CD49d+/high population recapitulated the             complexity of the original primary tumors. Greater doxorubicin resistance was             exhibited by the CD49d+/high population, compared with the CD49d-/low population.             Thus, our results collectively demonstrate that CD49d+/high cells from sarcospheres             display enhanced sphere-forming, drug resistance and tumor-initiating abilities.             To our knowledge, this is the first study to identify TICs from breast sarcoma.
authors.affiliation: Cancer Research Institute, Seoul National University College                     of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Jong Bin
authors.initials: JB
authors.lastname: Kim
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ko
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Dong Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Kuenhee
authors.initials: K
authors.lastname: Oh
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002273:Carcinogens / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D039441:Integrin alpha4; D004317:Doxorubicin