LUNG ENDOTHELIAL DIPEPTIDYL PEPTIDASE-IV PROMOTES ADHESION AND METASTASIS OF RAT BREAST-CANCER CELLS VIA TUMOR-CELL SURFACE-ASSOCIATED FIBRONECTIN

Endothelial cell adhesion molecules are partly responsible for the dis tinct organ distribution of cancer metastases. Dipeptidyl peptidase IV (DPP nr) expressed on rat lung capillary endothelia is shown here to be an adhesion receptor for rat breast cancer cells and to mediate lun g colonization by these tumor cells. Fibronectin (FN) assembled on bre ast cancer cell surfaces into multiple, randomly dispersed globules fr om cellular and plasma FN is identified as the principal ligand for DP P 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 ar e incubated with soluble DPP TV prior to conducting adhesion and lung colony assays. Adhesion is also blocked by anti-DPP IV monoclonal anti body 6A3 and anti-FN antiserum. However, adhesion to immobilized FN is unaffected by soluble plasma FN and, thus, can happen during hematoge nous spread of cancer cells at high plasma FN concentrations. The abil ity 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 mecha nism for lung metastasis.