For instance, matrix metalloproteinases (MMP-1, -2, -3, -9 and -13) cleave SPARC in vitro in its N-terminal acid domain and in its extracellular Ca2+ binding domain, releasing fragments with higher affinity for collagens that modulate cell-cell and cell-matrix extracellular interactions in the tumor microenvironment 58. The gene discussed is SPARC; the disease is neoplasm.