Biological and Molecular Characterization of a Model of Cancer Metastasis

Tannoch, Vivien J (1994) Biological and Molecular Characterization of a Model of Cancer Metastasis. PhD thesis, University of Glasgow.

Abstract

Metastatic disease represents the greatest cause of morbidity and mortality in most cancer patients. The process of metastasis appears complex and multifaceted and has still to be comprehensively understood. To investigate the metastatic phenotype, a murine model system was employed: the CMT model. The basis of this model is a pair of related epithelial cell lines which were both derived from the same spontaneous tumour in a C57B/T animal, but which exhibit markedly differing metastatic potentials. The CMT 167/C6 subline exhibits a high metastatic potential as measured in the spontaneous metastasis assay in syngeneic, immunocompetent C57B/T animals and the subline CMT 170/E9 exhibits low metastatic potential. Examination and characterization of these two cell lines revealed remarkably few differences between the cell lines. Decreased protein expressions of the cell adhesion molecules E-cadherin and NCAM were detected in CMT 167/C6 cells in comparison with CMT 170/E9 cells. Neither cell line secreted collagenases as assayed by zymography, nor did either cell line exhibit gap-junctional communication. Expression of the putative metastasis-associated gene mts-1 was not detected by Northern analysis in either cell line and expression of alternatively-spliced isoforms of CD44, which have been implicated in another metastasis model system, was not found. Examination of gene amplification by in-gel renaturation, which allows for the detection of reiterated DNA sequences without specific analysis of a particular gene, revealed no differences between the two cell lines which may be correlated with their differing metastatic phenotypes. The evidence presented suggests that metastasis as displayed in this model may result from a number of subtle alterations within the cell which may not be an "all-or-nothing" effect. This is supported from preliminary evidence of 2-D gel electrophoresis which detected few differences between the cell lines with apparently no resolved protein identified to be specifically expressed in either cell line; the preliminary identification of differences were quantitative in nature. Additionally, analysis of transcription factors in the CMT model revealed only subtle quantitative differences in EMSA experiments; qualitative differences were not observed. In this model, the most distinct differences found between the cell lines which may be significant to the differing metastatic phenotypes, were alterations in cell adhesion. The implications of these results and further experiments to examine this are discussed.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: George Birnie
• Keywords: Oncology, Molecular biology
• Date of Award: 1994
• Depositing User: Enlighten Team
• Unique ID: glathesis:1994-74910
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 15:13
• Last Modified: 27 Sep 2019 15:13
• URI: https://theses.gla.ac.uk/id/eprint/74910