Thesis

Effects of IGFBP-5 on epithelial and mesenchymal clones of NMuMG cells

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Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13210
Qualification Level
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Department, School or Faculty
Abstract
  • Epithelial mesenchymal transition is a developmental mechanism ensuring tissue remodelling during morphogenesis, but is also responsible for fibrosis and cancer. The aim of the project was to study the initial fibrotic regulating properties of IGFBP-5 in NMuMG cells using TGFβ-1 as a positive control. Adenovirus expressing IGFBP-5 at 600 MOI produced IGFBP-5 for several days, and showed that IGFBP-5 is lethal to NMuMG cells at higher doses. Short term adhesion experiments with exogenous IGFBP-5 and extracellular matrix components demonstrated that IGFBP-5 enhanced the spreading and adhesion of epithelial cells, while detaching the mesenchymal cells which aggregated into clusters having more cell contact. IGFBP-5 partially overcame the effects of TGFβ-1 when provided together, where it stimulated the migration of epithelial cells, but inhibited the TGFβ-1-induced mesenchymal cell migration. Phosphokinase array revealed contradictory, although preliminary information of enhanced activity of pro-survival pathways for the IGFBP-5 vector treated cells, along with a reduced expression of β-galactosidase enzyme. However none of the phosphokinase inhibitors tested were able to elucidate the role of intracellular signalling cascades mediating IGFBP-5 action in NMuMG cells, although they did define the role of Smad and Erk1/2 in TGFβ-1 induced fibroblast elongation. These results suggest that IGFBP-5 may drive short-term adhesion and survival responses in epithelial cells but induce death during longer-term expression. In addition IGFBP-5 has opposing effects on mesenchymal cells and antagonises the actions of TGFβ-1.
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Note
  • Strathclyde theses - ask staff. Thesis no. : T13210
DOI
Date Created
  • 2012
Former identifier
  • 947976

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