Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion
Journal article, 2005
To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-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 beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.
metabolism
Mice
Knockout
Neural Cell Adhesion Molecules
Gene Expression Profiling
Mice
metabolism
Inbred C57BL
metabolism
Biological
Mice
Cell Transformation
RNA
Disease Progression
genetics
pathology
Neoplastic
genetics
Messenger
Animals
Reverse Transcriptase Polymerase Chain Reaction
Tumor Markers
metabolism
Insulinoma
genetics
Oligonucleotide Array Sequence Analysis
physiology
Extracellular Matrix Proteins
Author
Joakim Håkansson
University of Gothenburg
Xiaojie Xian
University of Gothenburg
Liqun He
University of Gothenburg
Anders Ståhlberg
Chalmers, Chemical and Biological Engineering, Molecular Biotechnology
Sven Nelander
University of Gothenburg
Tore Samuelsson
University of Gothenburg
Mikael Kubista
Chalmers, Chemical and Biological Engineering, Molecular Biotechnology
Henrik Semb
University of Gothenburg
Tumor Biology
1010-4283 (ISSN) 1423-0380 (eISSN)
Vol. 26 2 103-112Subject Categories
Biochemistry and Molecular Biology
MEDICAL AND HEALTH SCIENCES
DOI
10.1159/000085817