CS/DS proteoglycans (PGs) consist of CS/DS chains attached to different core proteins. They play a recognized role in the extracellular matrix of host organ stroma, in tumor extracellular matrix, and on the cell surface of cancer cells (7). Functions of CS/DS-PGs in tumor progression can be attributed not only to the core proteins but also to the CS/DS chains. Removal of the CS/DS chains has been demonstrated to inhibit angiogenesis, proliferation, and invasion of melanoma cells (8). GlcAGalNAC(4-O- and 6-O-disulfated)-containing CS structures on the cell surface of lung carcinoma and osteosarcoma cells are important in the metastatic process (9, 10). In addition, IdoA-containing domains bind the fibroblast growth factors, FGF2 and FGF7, and hepatocyte growth factor (HGF) (11–13). HGF, together with its receptor c-MET are major players in cancer migration and invasion (14). Fibroblast-secreted HGF was shown to promote ESCC invasion through the c-MET receptor in an in vivo-like organotypic 3D cell culture (15). It is known that HGF bind DS in an in vitro (12), but, the functions of HGF binding to DS and its possible role in cancer are still unknown.
