Le(y) glycolipid-recognizing monoclonal antibody inhibits procoagulant activity and metastasis of human adenocarcinoma

Tumor procoagulant is associated with cancer at advanced stages of malignan cy such as infiltration and metastasis. In the present study, we investigat ed the role of Ley glycolipid in the mechanism of cancer metastasis. Ley gl ycolipid acts as an important cofactor in the expression of the blood-coagu lating, activity of cancer cell-derived coagulating activity I (CCA-1), whi ch is one of the known tumor procoagulants. Monoclonal antibody (MoAb) FS01 , which serves as the Le(y)-recognizing epitope, inhibits the procoagulant activity of CCA-1 was found to dose-dependently inhibit the procoagulant ac tivity of normal plasma induced by the human lung, adenocarcinoma cell line , HAL8, which shows a high level of Ley expression. It did not, however, in hibit the procoagulant activity of the human colon cancer cell line, RPMI47 88, which does not express Ley. Administration of FS01 MoAb inhibited lung metastasis of HAL8 cells, but not that of RPMI4788. The absence of antibody -dependent cellular cytotoxicity and complement-mediated cytotoxicity of FS 01 MoAb against the HAL8 cell line suggests that the inhibition of HAL8 met astasis by FS01 MoAb derives from the inhibition of blood-coagulating activ ity of the latter. These findings indicate that Ley glycolipid plays an imp ortant role in the mechanism of cancer metastasis via the procoagulant acti vity of CCA-1.