Human carcinoembryonic antigen (CEA) and the related CEA family member nonspecific cross-reacting antigen (NCA), function in vitro as intercellular adhesion molecules. Changes in the expression pattern of CEA and NCA in a wide variety of cancerous tissues has raised the possibility that they could contribute to neoplastic and malignant transformation by influencing tissue architecture and differentiation. This study revisits the expression pattern of CEA and NCA in colorectal tumorigenesis by emphasizing the accurate quantitation of cell-surface levels in the context of tissue architecture. FACSRTM analysis of highly purified tumor versus normal colonic epithelial cell suspensions, revealed dramatically higher levels of cell-surface associated CEA and NCA in tumor cells that was inversely correlated with histologic differentiation. Furthermore, a marked tendency towards delocalized expression and a multilayered tissue architecture was noted in less differentiated tumors. Increased levels of call-surface CEA and/or NCA (CEA/NCA) in colonocytes capable of differentiation was directly tested for effects on tissue architecture and differentiation with established in vitro assays and a novel in vivo colonic tissue architecture assay developed and presented as part of this thesis. The results demonstrate that overexpression of CEA/NCA on the surface of colonocytes can prevent cellular polarization, disrupt colonic tissue architecture and block differentiation both in vitro and in vivo.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35898 |
| Date | January 1998 |
| Creators | Ilantzis, Christian. |
| Contributors | Stanners, Clifford P. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650387, proquestno: NQ50189, Theses scanned by UMI/ProQuest. |
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