title: Aberrant Wnt/β-catenin signaling and elevated expression of stem cell proteins are associated with osteosarcoma side population cells of high tumorigenicity.
abstract: According to the cancer stem cell theory, the presence of a small sub‑population of cancer cells, termed cancer stem cells (CSCs), have a significant implication on cancer treatment and are responsible for tumor recurrence. Previous studies have reported that alterations in the Wnt/β‑catenin signaling are crucial in the maintenance of CSCs. In the present study, the characteristic features and activation of Wnt/β‑catenin signaling in CSCs from osteosarcoma, an aggressive human bone tumor, were investigated. In total, ~2.1% of the cancer stem‑like side population (SP) cells were identified in the osteosarcoma samples. The results of subsequent western blot and reverse transcription‑quantitative polymerase chain reaction analyses revealed that the protein levels of β‑catenin and cyclin D1 were markedly upregulated in the fluorescence‑activated cell sorted osteosarcoma SP cells. In addition, the elevated expression levels of stem cell proteins, including CD133, nestin Oct‑4, Sox‑2 and Nanog were significantly higher in the SP cells, which contributed to self‑renewal and enhanced the proliferation rate of the SP cells. Furthermore, the SP cells were found to be highly invasive and able to form tumors in vivo. Taken together, these data suggested that the identification of novel anticancer drugs, which suppress the Wnt/β‑catenin signaling and its downstream pathway may assist in eradicating osteosarcoma stem cells.
authors.affiliation: Department of Traumatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Yi
authors.affiliation: Department of Traumatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Zhao
authors.affiliation: Department of Traumatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Qiao
authors.affiliation: Department of Traumatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jin
authors.affiliation: Operating Room, Linyi Cancer Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Traumatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Qiu-Shi
authors.initials: QS
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051176:beta Catenin; D019938:Cyclin D1