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

Journal article
Authors Joakim Håkansson
Xiaojie Xian
Liqun He
Anders Ståhlberg
Sven Nelander
Tore Samuelsson
Mikael Kubista
Henrik Semb
Published in Tumour Biology
Volume 26
Issue 2
Pages 103-112
ISSN 1010-4283
Publication year 2005
Published at Institute of Medical Biochemistry
Pages 103-112
Language en
Keywords Animals, Cell Transformation, Neoplastic, Disease Progression, Extracellular Matrix Proteins, metabolism, Gene Expression Profiling, Insulinoma, metabolism, pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neural Cell Adhesion Molecules, genetics, physiology, Oligonucleotide Array Sequence Analysis, RNA, Messenger, genetics, metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tumor Markers, Biological, genetics, metabolism
Subject categories Medical and Health Sciences, Molecular biology


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.

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