Abstract
To elucidate the role of VLA-4 (alpha 4 beta 1 integrin) in tumor metastasis, we have transfected cDNA coding alpha 4 subunit into human fibrosarcoma (HT1080) cells. VLA-4-overexpressing HT-VC1 cells exhibited increased ability to interact with known ligands for VLA-4, such as CS1 peptide and VCAM-1 (vascular cell adhesion molecule-1). In addition, the in vitro invasive ability of HT-VC1 cells was augmented and the mRNA for type IV collagenase was increased in HT-VC1 cells. The induction of VCAM-1 molecules on lung endothelial cells of nude mice by tumor necrosis factor-alpha treatment resulted in augmentation of in vivo HT-VC1 cell adhesion to the lung endothelial cells. Thus, the VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cells, that is important for hematogenous metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal
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Cell Adhesion
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Cell Adhesion Molecules / metabolism*
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Collagenases / metabolism
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Extracellular Matrix Proteins / metabolism*
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Female
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Fibrosarcoma / metabolism
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Fibrosarcoma / pathology*
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Lung / metabolism
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Matrix Metalloproteinase 9
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Invasiveness / pathology*
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Neoplasm Metastasis / pathology*
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Receptors, Very Late Antigen / analysis
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Receptors, Very Late Antigen / genetics
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Receptors, Very Late Antigen / physiology*
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Cell Adhesion Molecule-1
Substances
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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Extracellular Matrix Proteins
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Receptors, Very Late Antigen
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Collagenases
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Matrix Metalloproteinase 9