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 (α4β1 integrin) in tumor metastasis, we have transfected cDNA coding z4 subunit into human flbrosarcoma (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‐α 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.