SPARC and the Tumor Microenvironment

Abstract

Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein that modulates the levels of cell adhesion and migration, as well as regulates cell proliferation, survival, and angiogenesis during normal development and tissue remodeling. These same cellular processes are necessary for tumor growth and progression, and they proceed as a result of the interplay between the tumor cells and the stromal and immune cells within the tissue microenvironment. Evidence suggests that SPARC contributes to these tumor-associated processes; however, deciphering its role is complicated by the fact that SPARC may be produced and secreted by cancer cells, stromal cells, and immune cells resulting in autocrine and paracrine effects on the tumor microenvironment. Its ability to promote deadhesion of cells from the ECM results in tumor and stromal cell migration and dissemination. It can also inhibit proliferation in cancer cells, fibroblasts, and endothelial cells directly or indirectly by binding to various growth factors and inhibiting downstream signaling. In addition, SPARC can regulate ECM deposition, assembly, and remodeling by regulating collagen processing and altering the secretion of matrix proteins and matrix degrading proteases from cancer cells and stromal cells. Finally, SPARC can also regulate the tumor microenvironment by suppressing immune cell infiltration and limiting tumor elimination. The evidence for each of these functions of SPARC in the regulation of the tumor microenvironment will be discussed.