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Studies on cellular adhesion molecules in colorectal cancer

Nigam, Anurag Kishore; (1999) Studies on cellular adhesion molecules in colorectal cancer. Doctoral thesis (M.D), UCL (University College London). Green open access

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Cell adhesion molecules are transmembrane receptors on the surface of cells that mediate interactions between cells and between cells and the extracellular matrix. They are involved in several physiological and pathological processes, including tumour invasion and metastasis. The aims of this thesis were to investigate a panel of cell adhesion molecules selected from the integrin, cadherin and immunoglobulin superfamilies in colorectal cancer. Changes in immunohistochemical localisation and degree of expression between normal and neoplastic colon were observed. The functional significance of altered expression in vivo was subsequently evaluated in adhesion assays and differentiation in collagen gel in vitro. Results showed that β1 and α2 integrins were consistently down-regulated in colorectal tumours. E-cadherin was lost in neoplastic tissue, particularly in poorly differentiated tumours, αv, αvβ3 and β5 integrins were localised to the stroma of tumours implying a possible role in the regulation of factors encouraging invasion and metastasis. Functional studies revealed α2β1 integrin to be the key integrin involved in the differentiation of a colorectal tumour cell line (SW1222) and therefore its loss in vivo correlating with the dedifferentiation seen in many of these tumours. Further studies centred on carcinoembryonic antigen (CEA), a protein related to the immunoglobulin superfamily of adhesion molecules. A colorectal cell line was transfected with the cDNA for CEA and NCA (nonspecific cross-reacting antigen), a member of the CEA family. Characterisation of CEA as an adhesion molecule revealed significant reduction in expression of [beta]1 integrins and E-cadherin in the transfectants compared to non-transfected cells. This was corroborated by functional data which revealed reductions in cell-matrix and cell-cell adhesion in transfectants. Tumorigenicity studies in nude mice revealed no alterations between parental and CEA transfectants. These investigations revealed that CEA acts in cellular adhesion by modulating the membrane expression of other key adhesion molecules, both phenotypically and functionally. These have secondary effects in the induction and maintenance of differentiation of cells and of signal transduction pathways important in the neoplastic process.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Studies on cellular adhesion molecules in colorectal cancer
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Transmembrane receptors
URI: https://discovery.ucl.ac.uk/id/eprint/10103958
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