Although HPSE is known to affect cell adhesion, including activation of β1 integrins, via both enzymatic and nonenzymatic means,7, 31, 32, 33, 34 myeloma spreading requires enzymatic activity because it is blocked by pre-treatment with the HPSE inhibitor Roneparstat35, 36, 37 (Figures 1a and b), and cannot be induced by enzymatically inactive HPSEM225 (ref. 15) overexpressed in the cells (Supplementary Figure S1). Here, HPSE is linked to plasma cell myeloma.