The main finding of this report is that tumor-promoting functions can be attributed to IdoA in DS chains. DS-epi1 and 2 are the enzymes responsible for conversion of GlcA to IdoA, and ultimately for the formation of DS. DS-epi1 is the main enzyme in vivo (16) and, because of its overexpression in most cancers, it has been suggested to be a cancer-associated antigen (2). In support of this idea, we found that DS-epi1 is highly expressed in ESCC cancer cells together with greater amounts of enzyme and increased DS-epimerase activity in cancer tissue as compared with normal tissue. Interestingly, we provide evidence that DS-associated IdoA appears to have a functional role in cancer cell behavior. Previous data suggest a synergistic effect of exogenously added DS and HGF in the stimulation of muscle cell proliferation and migration (28). The profound action of HGF on invasion has been demonstrated in a variety of cancer cells, including ESCC (15). DS and HGF could potentially form a receptor binding signaling complex in analogy with FGF2 and heparan sulfate (29, 30). Previous reports with different
