SPARC, a Matricellular Glycoprotein with Important Biological Functions

Abstract

SUMMARY SPARC (secreted protein, acidic and rich in cysteine) is a unique matricellular glycoprotein that is expressed by many different types of cells and is associated with development, remodeling, cell turnover, and tissue repair. Its principal functions in vitro are counteradhesion and antiproliferation, which proceed via different signaling pathways. SPARC consists of three domains, each of which has independent activity and unique properties. The extracellular calcium binding module and the follistatin-like module have been recently crystallized. Specific interactions between SPARC and growth factors, extracellular matrix proteins, and cell surface proteins contribute to the diverse activities described for SPARC in vivo and in vitro. The location of SPARC in the nuclear matrix of certain proliferating cells, but only in the cytosol of postmitotic neurons, indicates potential functions of SPARC as a nuclear protein, which might be involved in the regulation of cell cycle progression and mitosis. High levels of SPARC have been found in adult eye, and SPARC-null mice exhibit cataracts at 1-2 months of age. This animal model provides an excellent opportunity to confirm and explore some of the properties of SPARC, to investigate cataractogenesis, and to study SPARC-related family proteins, e.g., SC1/hevin, a counteradhesive matricellular protein that might functionally compensate for SPARC in certain tissues.

Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

“…SPARC is a matricellular protein with antiproliferative and counteradhesive functions (Yan and Sage, 1999). Its function in cancer is discussed in a very controversial manner (Clark and Sage, 2008;Podhajcer et al, 2008;Tai and Tang, 2008).…”

“…Secreted protein acidic and rich in cysteine (SPARC) or osteonectin is a 32 -33 kDa calcium-binding glycoprotein shown to associate with the cell membrane and membrane receptors (Yan and Sage, 1999). It belongs to a family of matricelluar proteins and is divided into three modules that exert various functions (Bradshaw and Sage, 2001).…”

“…Thus, in certain types of cancers, such as melanomas and gliomas, SPARC is associated with a highly aggressive tumour phenotype, whereas in others, mainly ovarian, neuroblastomas, and colorectal cancers, SPARC may function as a tumour suppressor . These functions are thought to be exerted in part by its ability to counteract effects of several growth factor families including fibroblast growth factors (FGFs) (Yan and Sage, 1999;Francki et al, 2003;Motamed et al, 2003).…”

CpG island methylation profile of pancreatic intraepithelial neoplasia

“…For example, reprimo is a downstream mediator of p53-induced G2 cell cycle arrest, and its overexpression induces cell cycle arrest at the G2 phase, suggesting that it has tumorsuppressor properties. 60 SPARC is a matricellular glycoprotein involved in diverse biological processes 61 and is frequently silenced by aberrant methylation in pancreatic adenocarcinomas. 23 Several lines of evidence suggest a tumor-suppressor role of SPARC in certain tumor types.…”

Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells

“…18 It is a noncollagenous, calcium-binding glycoprotein that has been mapped to the long arm of chromosome 5 19 and is related to wound healing 20 and angiogenesis. 21 We considered the three proteins to be potential targets for treatment in order to slow down or suppress the formation of bone metastasis. For a specific treatment, we identified antisense oligonucleotides (ASOs) that are capable of reducing the expression levels of OPN, BSPII and ON.…”