A novel secreted tumor antigen with a glycosylphosphatidylinositol-anchored structure ubiquitously expressed in human cancers

In a search for novel genes expressed in human cancers, we identified one g ene from an assembled expressed sequence tag database. Northern blot analys is revealed that the gene, termed alcan, was expressed in various types of human cancer cell lines and in the fetus, but not in normal tissues. The al can gene is located on chromosome 6 and is encoded on a 246-amino-acid prot ein with weak homology to classical major histocompatibility complex class I. Its gene product, ALCAN, had hydrophobic amino acid clusters at both the N- and C-terminal regions and was predicted to be a glycosylphosphatidylin ositol (GPI)anchored membrane protein. Flow cytometric analysis revealed th at ALCAN was detected on the surface of human cancer cells and on alcan-tra nsfected CHO-K1 cells. ALCAN was also secreted from these cells, suggesting that some portion of the molecules was secreted by enzymatic cleavage by, for example, phospholipases. Mutational analysis of ALCAN suggested that th e GPI-anchored position was the Ser(216) residue. These findings indicate t hat ALCAN may be a potential target for cancer diagnosis or therapy, (C) 20 01 Academic Press.