Human carcinoembryonic antigen (CEA) is the prototypic member of a large family of highly related cell surface glycoproteins that includes CEACAM6 (formerly NCA) and CEACAM1 (formerly BGP). The extracellular domains of CEA/CEACAM6 are bound to the external surface of the plasma membrane through a glycosylphosphatidyl inositol (GPI) anchor and are over-expressed in more than 50% of all human cancers. In contrast, CEACAM1 contains extracellular, transmembrane and cytoplasmic domains, and its level of expression is down-regulated in human tumors of the colon and prostate. When over-expressed on the surface of various cell types in model systems, CEA/CEACAM6, but not CEACAM1, function as pan-inhibitors of cell differentiation and cell polarization and cause a distortion of tissue architecture. Anoikis is a quality control mechanism that must be inhibited in cancer cells for such a distortion to persist. This thesis presents data demonstrating that CEA/CEACAM6 over-expression on the surface of a variety of cell lines inhibited anoikis. The molecular basis for the inhibitory effects of CEA/CEACAM6 on both anoikis and differentiation is shown to be correlated with perturbation of the function of certain integrins. In contrast to CEA/CEACAM6, the expression of the CEACAM1 glycoprotein neither perturbed integrin function nor prevented anoikis and, consistent with this, inhibited tumor growth. As a conclusion, we propose that CEA/CEACAM6, but not CEACAM1, over-expression on the surface of cancer cells inhibits cell differentiation and anoikis through perturbation of integrin functions. These inhibitory effects could instrumentally contribute to tumor formation and progression.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.37804 |
| Date | January 2000 |
| Creators | Ordoñez, Cosme. |
| Contributors | Stanners, Clifford (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: 001803225, proquestno: NQ70120, Theses scanned by UMI/ProQuest. |
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