SPARC is a phosphorylated, acidic, glycine-rich glycoprotein of 43 kD that is secreted by endothelial cells and is present in large amounts in the parietal endoderm of mouse embryos and in human placenta. It is homologous to bovine osteonectin, a major noncollagenous protein of bone, and has Ca(++)-binding domains. The function of this protein, conserved in evolution, is not known, but it may be involved in cell proliferation, repair of tissue damage, and morphogenetic processes such as modeling of extracellular matrix.
NCBI Summary:
This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2015]
Mok et al. (1996) cloned a SPARC homolog from the normal human ovarian surface epithelial (HOSE) cells and demonstrated that it is expressed at high levels in the normal HOSE cells but at much lower levels in ovarian carcinoma cells in vitro and in vivo. After transfection of the full length SPARC cDNA into an ovarian carcinoma cell line SKOV3 led to reduced growth rate of the cancer cell line in culture and reduced the cell's ability to induce tumours in nude mice. These results suggest that SPARC may play an important role in growth and and differentiation of the HOSE cells and support the hypothesis that SPARC functions as a tumor suppressor. Brown et al. (1999) compared the distribution of SPARC mRNA and protein expression in patient specimens of malignant and nonmalignant ovaries. High-level expression of SPARC mRNA and protein was detected in stroma of ovaries containing malignant tumor cells, particularly at the tumor-stromal interface of the invading tumors.
Cellular localization
Extracellular Matrix, Secreted
Comment
Ovarian function
Steroid metabolism, Luteinization
Comment
The expression, regulation and function of secreted protein, acidic, cysteine-rich (SPARC) in the follicle-luteal transition. Joseph C et al. The role of the tissue remodelling protein, secreted protein, acidic, cysteine-rich (SPARC) in key processes (e.g. cell re-organisation and angiogenesis) that occur during the follicle-luteal transition is unknown. Hence, we investigated the regulation of SPARC in luteinsing follicular cells and potential roles of SPARC peptide 2.3 in a physiologically-relevant luteal angiogenesis culture system. SPARC protein was detected mainly in the theca layer of bovine pre-ovulatory follicles, but its expression was considerably greater in the corpus haemorrhagicum. Similarly, SPARC protein (Western blotting) was up-regulated in luteinising granulosa but not theca cells during a 6-day culture period. Potential regulatory candidates were investigated in luteinising granulosa cells: LH did not affect SPARC (P>0.05); Transforming growth factor (TGF) B1 (P<0.001) dose-dependently induced the precocious expression of SPARC and increased final levels: this effect was blocked (P<0.001) by SB505124 (TGFB receptor 1 inhibitor). Additionally, fibronectin which is deposited during luteal development increased SPARC (P<0.01). In luteal cells, fibroblast growth factor 2 decreased SPARC (P<0.001) during the first five days of culture, while vascular endothelial growth factor A increased its expression (P<0.001). Functionally, KGHK peptide, a SPARC proteolytic fragment, stimulated the formation of endothelial cell networks in a luteal cell culture system (P<0.05) and increased progesterone production (P<0.05). Collectively, these findings indicate that SPARC is intricately regulated by pro-angiogenic and other growth factors together with components of the extracellular matrix during the follicle-luteal transition. Thus it is possible that SPARC plays an important modulatory role in regulating angiogenesis and progesterone production during luteal development.
Granulosa cells in the early vascularizing CL express SPARC. Neovascularization of CL was accompanied by expression of SPARC in nascent vessels. The observed changes in expression of SPARC and TSP during development of the CL support distinct
roles for these matricellular proteins in nonpathological morphogenesis and angiogenesis (Bagavandoss et al., 1998).
Expression regulated by
LH
Comment
Administration of a luteinizing stimulus (chorionic gonadotropin) increased the expression of SPARC in granulosa cells (Bagavandoss et al., 1998).
Neilson L, et al 200 reported molecular phenotyping of the human oocyte by PCR-SAGE.
Consecutive application of PCR and serial analysis of gene expression (SAGE) was used to generate a
catalog of approximately 50,000 SAGEtags from nine human oocytes. Matches for known genes were
identified using the National Institutes of Health SAGEtag database. Matches in the oocyte SAGE catalog
were found for surface receptors, second-messenger systems, and cytoskeletal, apoptotic, and secreted
proteins, including the SPARC gene decribed here.
Bagavandoss et al., 1998 characterized the expression of SPARC in postovulatory preluteal follicles and corpus luteum of hormone-primed immature rats. By indirect immunofluorescence with specific antibodies, SPARC was found in the cytoplasm of granulosa cells and thecal cells of preluteal follicles, in connective tissue cells of the ovarian interstitium, and in the oocyte nucleus. Furthermore, expression of SPARC messenger RNA (mRNA) was examined within ovine corpus luteum (CL) collected on days 3, 7, 10, 13, and 16 post estrus, and within pools of purified small and large luteal cells by Northern and dot blot analysis (Smith et al., 1996). Amounts of SPARC mRNA increased during the early luteal phase, peaked by day 7 and subsequently declined on days 10 and 13. SPARC mRNA content was significantly higher in the small than in the large cells. In situ hybridization showed that SPARC mRNA was localized to the thecal layer of Graafian follicles and to day 3 and day 10 CL. Within CL, immunohistochemistry indicated that SPARC protein was associated with small luteal cells but not with large cells. This specific localization to small cells was confirmed by
colocalization of SPARC with 3 beta-hydroxysteroid dehydrogenase.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
SPARC has been reported to be markedly down-regulated in ovarian carcinomas relative to the normal surface epithelium and has been suggested to act as a tumor suppressor in ovarian cancer.
Browm et al. (1999) reported that, in nonmalignant human ovaries, SPARC mRNA expression was restricted to thecal and granulosa cells of vessiculated follicles. Cytoplasmic SPARC immunoreactivity was observed in these compartments, whereas variable SPARC immunostaining was observed in normal surface epithelial cells. In contrast, high-level expression of SPARC mRNA and protein was detected in stroma of ovaries containing malignant tumor cells, particularly at the tumor-stromal interface of the invading tumors. Lower levels and a more diffuse pattern of SPARC mRNA expression were associated with LMP specimens. SPARC mRNA was not expressed by ovarian adenocarcinoma or by surface epithelial cells. Consistent with the in situ hybridization data, SPARC immunoreactivity was found throughout the reactive stroma of specimens containing ovarian carcinoma.