Novel extracellular sulfatases: Potential roles in cancer

The sulfation state of glucosamine residues within heparan sulfate proteoglycans (HSPGs) is known to be critical for the binding of many growth and differentiation factors and for signaling by some factors. Recently, we cloned two novel extracellular sulfatases (Sulf-1 and Sulf-2) in human and mouse (1) following the identification of orthologues of one of them in quail and rat. These sulfatases are distinct from classical intracellular sulfatases, which are mainly located in lysosomes and function in the breakdown of sulfated macromolecules. The novel sulfatases possess two regions of high homology to the human glucosamine-6-sulfatase. The Sulfs can function as endosulfatases against heparin. An interesting possibility is that the extracellular sulfatases have analogous functions during development and during tumor formation, i.e. regulating the bioavailability of heparin-binding growth/differentiation factors. Consistent with a role for the Sulfs in tumor formation, we have detected increased levels of Sulf mRNAs in several tumors compared to normal tissues.