Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis.

Abstract

The formation of secondary tumors by circulating cancer cells (blood-borne metastasis) correlates with an increased tendency of the cells to form emboli by aggregation with other tumor cells or with host cells. Although it is evident that cell-cell recognition and adhesion are mediated by cell surface components, the identity of these molecules is only now being unraveled. Over the last decade an increasing number of studies have demonstrated the presence of endogenous carbohydrate-binding proteins on the surface of various normal cells, and it has been proposed that such lectin-like molecules might be involved in intercellular adhesion. We have shown that various tumor cell lines contain endogenous galactose-specific lectins. Lectin activity was detected at the cell surface by the binding of asialofetuin. This glycoprotein also enhanced the aggregation of the tumor cells. After purification by affinity chromatography on immobilized asialofetuin the lectin activity was associated with two proteins of Mr 14,500 and 34,000. By using polyclonal and monoclonal antilectin antibodies in conjunction with various immunologic techniques we have demonstrated that the endogenous lectins are present on the surface of different tumor cells. Quantitation of cell surface lectins by flow cytometric analyses of antilectin antibody binding revealed that among related tumor cells those exhibiting a higher metastatic potential expressed more lectin on their surface. The binding of monoclonal antilectin antibodies to metastatic cells decreased asialofetuin-induced homotypic aggregation in vitro and suppressed the ability of the cells to form lung metastases after intravenous injection in the tail vein of syngeneic mice. These results strongly implicate the tumor cell surface lectins in cell adhesion and metastasis. We propose that such lectins can increase the ability of tumor cells that enter the blood stream to form aggregates with other tumor cells, or to adhere to host cells or the extracellular matrix and thereby increase their metastatic potential. Other contributing components to tumor cell-host cell interactions are cell surface carbohydrate-binding proteins that have been detected on lymphocytes, platelets, macrophages, hepatocytes, and endothelial cells. These lectin-like molecules might recognize and bind carbohydrates expressed on the surface of tumor cells and enhance emboli formation and organ colonization.