Year: 2006
Type: dissertation
Abstract: In the present thesis N-cadherin and its cleaved form soluble N-cadherin (sN-CAD) are studied in relation to cancer. Cadherins are calcium-dependent intercellular adhesion molecules that are often deregulated in cancer. E-cadherin, which is expressed by normal epithelial cells, is downregulated when cells become cancer cells and this sometimes coincides with transactivation of another cadherin, for example N-cadherin. As a result, cells change their phenotype and become fibroblastic, motile and invasive. The role of N-cadherin during cell adhesion, differentiation, embryogenesis and cancer is reviewed, and several examples are given of N-cadherin expression in tumour cell lines and biopsies. Extracellular proteases, also known as the cancer degradome, play an important role during tumour progression; they are involved in processes as invasion and metastasis but also cell proliferation, apoptosis and angiogenesis. The proteases, such as ADAM10, MT1-MMP and plasmin are able to shed a 90 kD extracellular fragment from N-cadherin. We could establish an ELISA for the detection of this sN-CAD. We tested body fluids from persons with no evidence of disease and cancer patients for the presence of sN-CAD. Significantly elevated levels of sN-CAD were measured in the cancer patient group and a weak but significant correlation was found with prostate specific antigen, which is the most frequently used circulating tumour marker for prostate cancer. Furthermore, sN-CAD also has a biological function: it was able to stimulate the motility of N-cadherin positive cells and more specifically of the endothelial cells. By using the chorioallantoic membrane assay and the rabbit corneal micropocket assay we could identify sN-CAD as a proangiogenic molecule. Unravelling the signalling pathway, we proved that the fibroblast growth receptor is an important player in the sN-CAD mediated effects. In conclusion, sN-CAD is a potentially interesting molecule in oncology, both as a circulating tumour marker and as a target for angiostatic treatment.
Author: Lara Derycke
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2298046686