HUMAN SERUM LECTIN - INDUCED APOPTOSIS AND METHOD FOR DETECTING APOPTOSIS

摘要

The unifying theme of the present invention is the description of a class of proteins present in human blood which have the capacity to selectively recognize and induce apoptosis of cells which convey abnormal surface carbohydrates. Alterations in cellular glycosylation can result from either species-specific differences or may reflect cancer-associated changes. Human serum carbohydrate binding proteins, referred to as lectins, were isolated on several different carbohydrate columns including Gal alpha (papGal), GalNAc, GlcNAc, Fucose, Mannose and Melibiose. These lectins were shown to cause apoptosis of porcine aortic endothelial cells. This demonstrates a new pathway leading to endothelial cell death following xenogenic stress that may be important in the pathogenesis of xenograft rejection and suggests new therapeutic approaches to the treatment of xenograft rejection. Further, these mammalian carbohydrate binding proteins are herein shown to cause apoptosis of breast cancer and lung cancer cells in vitro, and can be used as a cytotoxic agent against human tumour cells. Significantly, the proteins of the present invention exhibit minimal binding or reactivity against normally glycosylated human cells. This invention also relates to a novel bioassay for the detection and quantitation of cellular apoptosis in vitro, and to the utility of this assay for the identification and evaluation of compounds with potential apogenic activity.