Regulation of collagen type I production by ionizing radiation and transforming growth factor-β1 in primary human skin fibroblasts derived from early stage breast cancer patients in relation to acute radiation-induced toxicity

  • Author / Creator
    Wang, Ying Wang
  • Regulation of collagen type I (CI) in fibroblasts is critical for the onset and development of skin toxicities induced by radiation therapy (RT). Transforming growth factor beta-1 (TGF-β1) and vascular endothelial growth factor (VEGF) promote CI synthesis, while its degradation is modulated by matrix metalloproteinase-1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1) and cathepsin K. We investigated the effects of ionizing radiation (IR) and/or TGF-β1 on CI levels and factors involved in CI regulation in primary skin fibroblasts derived from 40 early stage breast cancer patients. We determined statistical relationships between CI levels and acute skin toxicity events in the same patients after RT. We found that inhibition of collagenolytic activity by TIMP-1 affects CI levels in response to TGF-β1 and/or IR treatment of primary human fibroblasts, and increased patient-derived fibroblast CI levels in response to ex-vivo IR could be predictive of acute RT-induced toxicities in patients.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Oncology
  • Supervisor / co-supervisor and their department(s)
    • Abdulkarim, Bassam (Oncology)
  • Examining committee members and their departments
    • Godbout, Roseline (Oncology)
    • Murray, David (Oncology)
    • Ghahary, Aziz (Surgery, University of British Columbia)
    • Sabri, Siham (Oncology)
    • Pasdar, Manijeh (Cell Biology)