Lung Endothelial Dipeptidyl Peptidase IV Promotes Adhesion and Metastasis of Rat Breast Cancer Cells via Tumor Cell Surface-associated Fibronectin

Abstract

Endothelial cell adhesion molecules are partly responsible for the distinct organ distribution of cancer metastases. Dipeptidyl peptidase IV (DPP IV) expressed on rat lung capillary endothelia is shown here to be an adhesion receptor for rat breast cancer cells and to mediate lung colonization by these tumor cells. Fibronectin (FN) assembled on breast cancer cell surfaces into multiple, randomly dispersed globules from cellular and plasma FN is identified as the principal ligand for DPP IV. Ligand expression correlates quantitatively with the tumor cells' capabilities to bind to DPP IV and to metastasize to the lungs. DPP IV/FN-mediated adhesion and metastasis are blocked when tumor cells are incubated with soluble DPP IV prior to conducting adhesion and lung colony assays. Adhesion is also blocked by anti-DPP IV monoclonal antibody 6A3 and anti-FN antiserum. However, adhesion to immobilized FN is unaffected by soluble plasma FN and, thus, can happen during hematogenous spread of cancer cells at high plasma FN concentrations. The ability of many cancer cells to capture FN molecules on their surface and to augment such deposits by FN self-association during passage in the blood suggests that DPP IV/FN binding may be a relatively common mechanism for lung metastasis.