Discoidin Domain Receptor-1a (DDR1a) Promotes Glioma Cell Invasion and Adhesion in Association with Matrix Metalloproteinase-2
Autor: | Roman Urfer, Karoly Nikolich, Gustavo Lorente, Erik Foehr, Rosalyn Ram, Usha Nagavarapu |
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Rok vydání: | 2005 |
Předmět: |
Cancer Research
Blotting Western Cell Biology Transfection Extracellular matrix Cell surface receptor Cell Line Tumor Glioma Cell Adhesion medicine Humans Immunoprecipitation Protein Isoforms Neoplasm Invasiveness Cell adhesion Discoidin Domain Receptors Oligonucleotide Array Sequence Analysis DDR1 Brain Neoplasms Receptor Protein-Tyrosine Kinases medicine.disease Immunohistochemistry Enzyme Activation medicine.anatomical_structure Neurology Oncology Ectodomain Receptors Mitogen Cancer research Matrix Metalloproteinase 2 Neurology (clinical) Discoidin domain |
Zdroj: | Journal of Neuro-Oncology. 76:239-248 |
ISSN: | 1573-7373 0167-594X |
Popis: | Invasion of glioma cells involves the attachment of invading tumor cells to extracellular matrix (ECM), disruption of ECM components, and subsequent cell penetration into adjacent brain structures. Discoidin domain receptor 1 (DDR1) tyrosine kinases constitute a novel family of receptors characterized by a unique structure in the ectodomain (discoidin-I domain). These cell surface receptors bind to several collagens and facilitate cell adhesion. Little is known about DDR1 expression and function in glioblastoma multiforme. In this study we demonstrate that DDR1 is overexpressed in glioma tissues using cDNA arrays, immunohistochemistry and Western blot analysis. Functional comparison of two splice variants of DDR1 (DDR1a and DDR1b) reveal novel differences in cell based glioma models. Overexpression of either DDR1a or DDR1b caused increased cell attachment. However, glioma cells overexpressing DDR1a display enhanced invasion and migration. We also detect increased levels of matrix metalloproteinase-2 in DDR1a overexpressing cells as measured by zymography. Inhibition of MMP activity using MMP inhibitor suppressed DDR1a stimulated cell-invasion. Similarly, an antibody against DDR1 reduced DDR1a mediated invasion as well as the enhanced adhesion of DDR1a and DDR1b overexpressing cells. These results suggest that DDR1a plays a critical role in inducing tumor cell adhesion and invasion, and this invasive phenotype is caused by activation of matrix metalloproteinase-2. |
Databáze: | OpenAIRE |
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