Active-β-catenin (ABC) Transcriptional Activity is Associated with and may Promote Invasive Phenotype in Osteosarcoma (OS)

• Author / Creator

  Landry, Takaaki

• Osteosarcoma (OS) is an aggressive primary malignancy of the bone with the greater proportion of affected individuals being in the 10-30 years age range. The 5-year relative survival rates for patients with localized OS is 77% and 27% for patients with metastatic cancer. 15-20% of patients on initial diagnosis present with metastasis of OS. Identifying reliable prognostic biomarkers to facilitate early diagnosis and appropriate treatment strategies is crucial. The canonical Wnt/β-catenin pathway has been shown to be dysregulated in OS. I investigated the role that the Wnt/β-catenin pathway may have in the promotion of the invasive phenotype. Specifically, I focussed on the transcriptionally active form of β-catenin, Active-β-Catenin (ABC) and whether it may have a role in the promotion of invasive phenotype.I used two sets of paired cell OS cell lines, SaOS2/SaOS2-LM7 and HOS/HOS-143B. I transfected the SaOS2 and HOS cell line with a pEGFP-C2-β-catenin fusion construct plasmid, or the pEGFP-C2-ABC plasmid which mimicked endogenous ABC. Using pEGFP-C2 (empty vector), pEGFP-C2-β-catenin, and pEGFP-C2-ABC I transfected the SaOS2 and HOS cells to measure what affect overexpression of ABC and β-catenin had on the overall invasive phenotype. My in vitro results show that ABC increased the invasive abilities of the SaOS2 and HOS cells, increased migratory abilities in SaOS2 cells, and increased mRNA expression of MMP9 and MMP2 in SaOS2 and HOS cells. Our analysis on the OS pediatric patient tissues showed a positive association between high levels of ABC and metastatic tumors of OS patients at both times of diagnosis and resection. These results suggest that ABC influences the invasive phenotype seen in OS progression and that ABC has the potential to be used as a prognostic biomarker in OS.

• Subjects / Keywords

  • Active beta-catenin
  • Osteosarcoma
  • Metastasis
  • Invasion

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-nj6p-c552

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.