There are three forms of enzymatic remodeling of heparan sulfate proteoglycans that are known to occur in myeloma, and other tumors, sulfatases, sheddases, and heparanase, which are active within the tumor microenvironment, point out the importance of regulated remodeling of heparan sulfate proteoglycans [216, 281–284]. This evidence concerns the gene CD44 and plasma cell myeloma.