Cytotoxic Effects of Lectins

Abstract

The interaction of lectins with various normal or malignant cells not infrequently results in their proliferation or death (1-3). Incubation of normal T-lymphocytes with some lectins, such as Con A and PHA stimulates their proliferation and renders them highly cytotoxic and capable of lysing various cell targets (4). This phenomenon is known as lectin-dependent cell cytotoxicity (LDCC). However, several lectins have been found to be able to kill various normal and malignant cells in the absence of lymphocytes. This type of lectinmediated cell lysis is obviously distinguishable from LDCC and can be termed direct lectin cytotoxicity The cytotoxic properties have been found with some lectins such as Con A, PHA, WGA, GSlA₄, GSlB₄, lens culinaris (LCA), ricin (RIC), and abrin lectins (2,3,5). Cells that survived after exposure to the cytotoxic lectins manifested resistance to cytotoxic activity of the same lectin. Numerous lectin-resistant sublines were isolated from the original lectin-sen-sitive cell lines. These lectin-resistant variants were widely used for the analysis of mechanisms of lectin resistance or sensitivity, and of glycoprotein and glycolipid biosynthesis in mammalian cells, the investigation of the biological role of cell surface carbohydrates in cell-to-cell interactions, and in regulation of metastatic behavior of malignant cells (2,6) For many cultured cell lines, the frequency of lectin-resistant variants was found to be about 10^-5– 10^-6. Some cell lines require mutagenization in order to obtain lectin-resistant cell variants (2). Analysis of mechanisms responsible for resistance to cytotoxic action of lectins revealed that, in some cases, lectin-resistant variants appeared as a result of loss of a specific glycosyltransferase activity with a consequent loss of the particular cell surface carbohydrate necessary for lectin binding (2). However, some lectin-resistant variants showed no loss of cell-surface carbohydrates, lectin binding, or cell agglutination (2) This might indicate that resistance of tumor cells to lectin cytotoxicity is not solely based on the loss of cell surface carbohydrates reacting with this lectin and that some postbinding events are probably involved in determining cell sensitivity to lectin cytotoxicity.