Neural cell adhesion molecule-deficient β-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion

To understand by which mechanism neural cell adhesion molecule (N-CAM) limits tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during tumour cell progression by gene expression profiling. Here, we show that N-CAM- deficient - 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. NCAM 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 tumour cell progression. Prospective consequences of these findings for the role of N-CAM in tumour cell dissemination are discussed. Copyright (C) 2005 S. Karger AG, Basel.