In addition to CAFs, tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs) support cancer invasion through ECM degradation via the secretion of MMPs.118 In addition, they secrete osteonectin, promoting tumor cells and ECM interaction.119 Further ECM remodeling is driven by TAM- and TAN-derived factors such as elastases, cathepsins, and proteinases-3.120,121 Changes in the bone microenvironment fuel the invasion process. The gene discussed is SPARC; the disease is neoplasm.