HPSE and neoplasm: Tumor-cell-derived factors include osteopontin (OPN), which promotes bone marrow cell migration and tumor cell proliferation; heparanase (HPSE), which alters the extracellular matrix by reducing the length of the heparan sulfate chain, increasing bone resorption; and parathyroid-hormone-related protein (PTHrP), which promotes bone resorption and may also increase bone marrow chemokines like C-C motif ligand 2 (CCL2).