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.