Document Details
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Document Type |
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Thesis |
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Document Title |
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The Role Of E-Cadherin in Modulating the Behavioural Characteristics of Oral Squamous Carcinoma Cells The Role Of E-Cadherin in Modulating the Behavioural Characteristics of Oral Squamous Carcinoma Cells |
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Document Language |
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English |
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Abstract |
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The incipient invasion of epithelial tumour cells, characterised by disruption of normal cell-cell adhesion, marks the point of transition to malignancy. Cadherins are a family of calcium-dependent, transmembrane, cell-cell adhesion molecules whose function requires association with the actin cytoskeleton of the cell through cytoplasmic proteins called catenins. Oral keratinocytes express E-cadherin, which is considered a regulator of the epithelial phenotype. Loss of E-cadherin commonly is seen in oral squamous cell carcinoma (OSCC), particularly in poorly differentiated tumours, allowing cells to detach from the tumour mass, invade and metastasise.
An E-cadherin negative OSCC cell line was identified where E-cadherin expression and function was restored through cDNA transfection resulting in functional cell surface expression of the protein and the formation of cell-cell attachments, with significant alteration in levels and distribution of catenins. Alteration of cell morphology, from a spindle to an epitheloid form, was observed. Additionally, restoration of E-cadherin showed a marked inhibition of the invasive potential of this OSCC cell line. These effects were not observed in the control cell line transfected with the expression vector containing antisense E-cadherin cDNA.
Most findings in cell and molecular biology, presented in the literature, are based, primarily, on in vitro studies obtained from the culture of cells growing in 2-dimensional (2-D) tissue culture dishes. In this study I have investigated if E-cadherin plays a role in modulating tumour cell growth in a 3-D, as opposed to a 2-D, environment. Results showed that the epitheloid-like morphology brought about by E-cadherin expression under 2-D conditions allows differences in density dependent inhibition to occur accompanied by enhancement in the apoptotic capacity of the cells. However, where constraints of 3-D culture are imposed, these variations between E-cadherin expressing and non-expressing lines disappear. To explore the basis of these changes I have examined Western blot analysis of proteins known to play a role in mediating cell proliferation or regulation of apoptosis, such as Bcl-2, Akt-1, ILK and N-cadherin. I showed that changes in levels of expression of these proteins under 2-D conditions is markedly affected when cells were implanted in 3-D collagen I cultures.
I also investigated the possible molecular cross talk between E-cadherin and the β4-integrin subunit. Results obtained from β4-knock-down experiments showed that β4-integrin plays a role in the maturation of E-cadherin-dependent cell-cell contacts. I investigated the possible mechanisms of this apparent cadherin-integrin cross-talk and preliminary results showed that the function of β4-integrin was, potentially, executed through the Rac1 small Rho GTPase. |
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Supervisor |
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Prof. Ian Hart |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1425 AH
2005 AD |
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Co-Supervisor |
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Dr. Gareth Thomas |
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Added Date |
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Wednesday, October 27, 2010 |
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Researchers
| سهر بخاري | Bukhary, sahar | Researcher | Doctorate | |
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