INHIBITION OF CELL ATTACHMENT, INVASION AND METASTASIS OF HUMAN CARCINOMA-CELLS BY ANTI-INTEGRIN BETA-1 SUBUNIT ANTIBODY

We investigated the expression of beta1 integrins in human carcinoma cell lines, and the anti-metastatic and anti-invasive effects of a newly established anti-human beta1 subunit monoclonal antibody designated NCC-INT-7. All the examined carcinoma cell lines expressed beta1 integrins upon immunoblot analysis. NCC-INT-7 completely inhibited the adhesion of carcinoma cells to laminin, fibronectin, collagens and acetone-fixed tissues including lung, liver and brain. In an in vitro invasion model, NCC-INT-7 inhibited the invasion of human bladder carcinoma cell line T24 and human gastric carcinoma cell lines TMK-1, MKN-45 and MKN-74 through an artificially reconstructed basement membrane. In an in vivo nude mouse peritoneal dissemination model using MKN-45 and TMK-1, NCC-INT-7 significantly reduced the number of tumor nodules in the mesentery. In an in vivo nude mouse liver metastasis model using a serially transplantable human colonic carcinoma, COL-2-JCK, NCC-INT-7 significantly reduced the number of tumor nodules in liver. These results indicate that beta1 integrins play an important role in the tissue attachment, migration, invasion and metastasis of human carcinoma cells, and that this new monoclonal antibody is useful for studies aimed at prevention of metastasis.