The role of blood group antigens in malignant progression, apoptosis resistance, and metastatic behavior

Abstract

T HE METASTATIC phenotype is an extremely complex biologic phenomenon comprising multiple biologic features such as matrix-independent growth and survival, motility, invasion, aberrant adhesive behavior, induction of neoangiogenesis, and apoptosis resistance. Correlation of metastatic human cancer with the expression of certain blood group carbohydrates or corresponding cell surface lectins is well established for several major types of human malignancies, such as colon, breast, and prostate cancers. Similar data are beginning to emerge for many other types of human cancer. It is well documented that bloocl group carbohydrates expressed on the cell surface of metastatic cancer cells function as cell adhesion molecules. The homotypic and heterotypic cell-cell adhesion mediated by interactions of certain blood group carbohydrates with corresponding lectins is a critically important event at the extravasation step of the metastatic cascade when metastatic cancer cells escape from the circulation into distant sites of secondary tumor growth. These adhesive interactions are believed to be essential for matrixindependent survival of blood-borne cancer cells. We describe initial experimental evidence that supports the hypothesis that carbohydrate-lectin interactions trigger an intracellular signaling cascade culminating in alterations of transcriptional control of gene expression. Furthermore, modification of gene expression triggered by carbohydratelectin interactions is manifested in differential gene expression profiles that distinguish highly and poorly metastatic cancer cells and may be responsible for matrix-independent survival and apoptosis resistance of metastatic cancer cells. Thus, the