VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cell surface.
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.
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D017364:Collagenases; D020780:Matrix Metalloproteinase 9