EXT2 and neoplasm: Furthermore, a catalytic interaction between Shh and HSPGs that affects non-cell autonomous signaling would provide significant new insights in developmental and tumor-inducing mechanisms, including the roles of Ext1 and Ext2 as tumor suppressors [56], roles of Gpcs as tumor suppressors [57, 58] a role for extracellular calcium as an inhibitor of Shh that contributes to Shh-mediated morphogenesis, or that affects tumor formation or progression, and a requirement for μM amounts of zinc for Shh activity in general.