SPARC (secreted protein acidic and rich in cysteine, Osteonectin, BM-40) is a matricellular glycoprotein that modulates cellular interactions with the ECM and is expressed in tissues undergoing remodeling. It functions as a de-adhesive protein, as a modulator of growth factor activity, and as a cell-cycle inhibitor. It induces changes in endothelial cell shape via F-actin, coincident with the appearance of intercellular gaps, that provide a paracellular pathway for extravasation of macromolecules. Tumor growth is enhanced in mice lacking SPARC due to changes in the ECM that create a more permissive environment for tumor progression. Additionally, SPARC is overexpressed in breast, prostate, colorectal and other cancers, and high expression of SPARC is a marker of poor prognosis in rectal cancer. In immunohistochemistry of normal tissue, SPARC has cytoplasmic positivity in endothelial cells, megakaryocytes, fibroblasts, some glial cells, seminiferous ducts of the testes, and neurons in the brain. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Cancer Biomark. 2017;18(4):459-466, PMID: 28009327;