Neural Cell Adhesion Molecule-Deficient β-Cell Tumorigenesis Results in Diminished Extracellular Matrix Molecule Expression and Tumour Cell-Matrix Adhesion

Abstract

To understand by which mechanism neural cell adhesion molecule (N-CAM) limits β tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during β tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient β-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient β tumour cell progression. Prospective consequences of these findings for the role of N-CAM in β tumour cell dissemination are discussed.