title: Enrichment of osteosarcoma stem cells by chemotherapy.
abstract: Osteosarcoma is the most common primary malignant bone cancer in children and adolescents. Emerging evidence has suggested that the capability of a tumor to grow is driven by a small subset of cells within a tumor, termed cancer stem cells (CSCs). Although several methods have been explored to identify or enrich CSCs in osteosarcoma, these methods sometimes seem impractical, and chemotherapy enrichment for CSCs in osteosarcoma is rarely investigated. In the present study, we found that short exposure to chemotherapy could change the morphology of osteosarcoma cells and increase sarcosphere formation in vitro, as well as increase tumor formation in vivo. Furthermore, methotrexate (MTX)-resistant U2OS/MTX300 osteosarcoma cells were larger in size and grew much more tightly than parental U2OS cells. More importantly, U2OS/MTX300 cells possessed a higher potential to generate sarcospheres in serum-free conditions compared to parental U2OS cells. Also, U2OS/MTX300 cells exhibited the side population (SP) phenotype and expressed CSC surface markers CD117 and Stro-1. Notably, U2OS/MTX300 cells showed a substantially higher tumorigenicity in nude mice relative to U2OS cells. Therefore, we conclude that chemotherapy enrichment is a feasible and practical way to enrich osteosarcoma stem cells.
authors.affiliation: Department of Musculoskeletal Oncology, Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China.
authors.forename: Qing-Lian
authors.initials: QL
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Xian-Biao
authors.initials: XB
authors.lastname: Xie
authors.forename: Jun-Qiang
authors.initials: JQ
authors.lastname: Yin
authors.forename: Chang-Ye
authors.initials: CY
authors.lastname: Zou
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Shen
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D000964:Antimetabolites, Antineoplastic; C525591:STRO-1 antigen, human; D019009:Proto-Oncogene Proteins c-kit; D008727:Methotrexate