Aberrant Wnt/β-catenin signaling and elevated expression of stem cell proteins are associated with osteosarcoma side population cells of high tumorigenicity

• Published in: Molecular medicine reports Vol. 12; no. 4; pp. 5042 - 5048
• Main Authors: YI, XI-JUN, ZHAO, YU-HUA, QIAO, LI-XIANG, JIN, CHUN-LEI, TIAN, JING, LI, QIU-SHI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: AC133 Antigen; Adult; Analysis; Animals; Antibiotics; anticancer drugs; Antigens, CD - genetics; Antigens, CD - metabolism; Antineoplastic Agents; Antineoplastic drugs; Antitumor agents; Apoptosis; beta Catenin - genetics; beta Catenin - metabolism; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cancer; cancer stem cell; Cell proliferation; Cell self-renewal; Cellular signal transduction; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Development and progression; Drug resistance; Drug Resistance, Neoplasm - genetics; Female; Gene Expression Regulation, Neoplastic; Glycoproteins - genetics; Glycoproteins - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Invasiveness; Male; Metastasis; Mice; Mice, SCID; Middle Aged; Nanog Homeobox Protein; Neoplasm Grading; Neoplasm Invasiveness; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nestin; Notch1; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Penicillin; Peptides - genetics; Peptides - metabolism; Physiological aspects; Polymerase chain reaction; Population; Primary Cell Culture; Reverse transcription; Sarcoma; self-renewal; Side-Population Cells - drug effects; Side-Population Cells - metabolism; Side-Population Cells - pathology; Signal transduction; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem cells; Tumorigenesis; Tumorigenicity; Tumors; Wnt protein; Wnt Signaling Pathway; Xenograft Model Antitumor Assays; β-Catenin; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.4025

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.