SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury

Bradshaw, Amy D.; Sage, E. Helene

doi:10.1172/jci12939

Cited by 578 publications

(544 citation statements)

References 29 publications

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“…Later, SPARC is ideally positioned to play a role in the formation and maintenance of the basal lamina that is necessary for Schwann cell myelination (Fig. 6) (Court et al, 2006), similar to its role in basement membranes in other tissues and across multiple organisms (Fitzgerald and Schwarzbauer, 1998;Huynh et al, 2000;Bradshaw and Sage, 2001;Martinek et al, 2002). This may also explain why oligodendrocytes, whose myelin does not have a basal lamina, do not express SPARC.…”

Section: Discussionmentioning

confidence: 97%

“…SPARC can be secreted to regulate local growth factor, ECM, and matrix metalloproteinase (MMP) activity, to modulate cell morphology and migration responses, angiogenesis, and cell proliferation and survival (Rempel et al, 2001;Francki et al, 2004;Barker et al, 2005a;Yan et al, 2005;Said et al, 2007a). In vitro, SPARC acts on many cell types as a deadhesive factor that induces cell rounding and inhibits cell migration (Sage et al, 1989b;Bradshaw and Sage, 2001), including on neuronal and glial cell lines (Ikemoto et al, 2000). However, SPARC is thought to act in vivo as a contextual regulator of cellular adhesion strength (Greenwood and Murphy-Ullrich, 1998), and is required for fibroblast migration during dermal wound healing (Basu et al, 2001), leukocyte infiltration after immune challenge (Kelly et al, 2007;Rempel et al, 2007), and tumor invasiveness (Rempel et al, 2001;Framson and Sage, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The SVZ contains specialized structures of extravascular basal lamina, termed fractones, that contain laminin and collagen (Mercier et al, 2002). As a highly conserved base- ment membrane molecule (Fitzgerald and Schwarzbauer, 1998;Bradshaw and Sage, 2001;Martinek et al, 2002), SPARC may be involved in the assembly and maintenance of fractones by regulating the production of ECM molecules such as laminin (Kamihagi et al, 1994;Weaver et al, 2006) and collagen (Francki et al, 1999;Bradshaw et al, 2003b). Ultrastructural examination of SPARC in the SVZ will be necessary to investigate this possibility further.…”

Section: Discussionmentioning

confidence: 99%

“…SPARC is highly expressed during embryogenesis and is restricted in the adult to tissues undergoing remodeling, repair, and tumorigenesis (Holland et al, 1987;Sage et al, 1989a;Bradshaw and Sage, 2001;Framson and Sage, 2004). SPARC is a multifunctional protein that regulates extracellular matrix (ECM) organization and cell-ECM interactions, leading to the modulation of cell adhesion and migration, promotion of cell survival, and inhibition of cell proliferation (Brekken and Sage, 2000).…”

Section: Introductionmentioning

confidence: 99%

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SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

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SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed during development, tissue remodeling, and repair. SPARC produced by olfactory ensheathing cells (OECs) can promote axon sprouting in vitro and in vivo. Here, we show that in the developing nervous system of the mouse, SPARC is expressed by radial glia, blood vessels, and other pial-derived structures during embryogenesis and postnatal development. The rostral migratory stream contains SPARC that becomes progressively restricted to the SVZ in adulthood. In the adult CNS, SPARC is enriched in specialized radial glial derivatives (Mü ller and Bergmann glia), microglia, and brainstem astrocytes. The peripheral glia, Schwann cells, and OECs express SPARC throughout development and in maturity, although it appears to be down-regulated with maturation. These data suggest that SPARC may be expressed by glia in a spatiotemporal manner consistent with a role in cell migration, neurogenesis, synaptic plasticity, and angiogenesis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

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“…In addition to its counteradhesive and antiproliferative functions, SPARC modulates angiogenesis and regulates the production, assembly and organization of the extracellular matrix (Sage et al, 1984;Bradshaw and Sage, 2001). The role of SPARC in tumorigenesis is complex and appears to be cell-type specific owing to its diverse functions in a given microenvironment.…”

Section: Introductionmentioning

confidence: 99%

SPARC enhances tumor stroma formation and prevents fibroblast activation

et al. 2007

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Tumor growth is influenced by interactions between malignant cells and the tumor stroma. Although the normal host microenvironment is nonpermissive for neoplastic progression, tumor-reactive stroma, characterized by the presence of activated fibroblasts, promotes neoplastic growth and metastasis. Secreted protein, acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is capable of inhibiting the growth of several different types of cancer. Recently, we reported that SPARC also impairs the growth of xenografts comprised of 293 cells. In this study, we show that in addition to enhancing stroma formation, SPARC prevents fibroblast activation in 293 xenografts, suggesting that the anticancer effects of SPARC may be due, at least in part, to the formation of tumor stroma that is not supportive of tumor growth. In vitro, 3T3 fibroblasts cocultured with SPARC-transfected 293 cells remain negative for a-smooth muscle actin, whereas wild-type 293 cells induce fibroblast activation. Moreover, activation of 3T3 cells and primary fibroblasts by transforming growth factor b is blocked by SPARC treatment. We also demonstrate that SPARC significantly increases basic fibroblast growth factor-induced fibroblast migration in vitro, indicating that it may recruit host fibroblasts to the tumor stroma. Taken together, our results suggest that in addition to blocking angiogenesis, SPARC may inhibit tumor growth by promoting the assembly of stroma that is nonpermissive for tumor progression.

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Basement Membrane ProteinBM‐40

Hohenester

Timpl

2004

Handbook of Metalloproteins

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BM‐40, also known as SPARC or osteonectin, is a secreted glycoprotein present in all metazoa. The protein is expressed in tissues undergoing morphogenesis, remodeling, and repair. In vitro , BM‐40 binds to several collagens and is both antiproliferative and counteradhesive. Human BM‐40 consists of an acidic N‐terminal domain, a follistatin‐like (FS) domain, and an α‐helical (EC) domain that contains two functional EF‐hand calcium‐binding motifs. The crystal structure of the FS–EC domain pair has been determined. Calcium and collagen binding to the EC domain has been studied using site‐directed mutagenesis, spectroscopy, and binding assays.

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SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury

Cited by 578 publications

References 29 publications

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

SPARC enhances tumor stroma formation and prevents fibroblast activation

Basement Membrane ProteinBM‐40

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