A prototypic matricellular protein in the tumor microenvironment—Where there's SPARC, there's fire

Clark, Clancy J.; Sage, E. Helene

doi:10.1002/jcb.21688

Cited by 115 publications

(111 citation statements)

References 100 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…A number of activities associated with SPARC have been described in cultured cells, including effects on cell proliferation and adhesion (11). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

Harris

Zhang²,

Card³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Harris BS, Zhang Y, Card L, Rivera LB, Brekken RA, Bradshaw AD. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces. Am J Physiol Heart Circ Physiol 301: H841-H847, 2011. First published June 10, 2011; doi:10.1152/ajpheart.01247.2010.-Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [ 3 H]proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-␣ 1(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production. extracellular matrix; fibrosis; matricellular; osteonectin; secreted protein acidic and rich in cysteine THE COLLAGEN CONTENT of the cardiac interstitium is tightly regulated to preserve the form and function of the heart. Collagen in the healthy heart aligns myocytes and provides structural support; however, increased collagen deposition in response to myocardial infarction or in some types of cardiac hypertrophy can impair heart function (2, 18, 31). For example, an increase in collagen concentration is associated with chronic pressure overload, such as that seen in individuals with arterial hypertension, and is frequently associated with impaired diastolic function (14). The increase in cardiac collagen has been shown to be a significant contributor to greater diastolic stiffness (31). Increases in interstitial fibrill...

show abstract

“…A number of activities associated with SPARC have been described in cultured cells, including effects on cell proliferation and adhesion (11). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

Harris

Zhang²,

Card³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Its function in cancer is discussed in a very controversial manner (Clark and Sage, 2008;Podhajcer et al, 2008;Tai and Tang, 2008). In certain types of cancers, such as melanomas and gliomas, SPARC is associated with a highly aggressive tumour phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…It functions not only to modulate cell -cell and cell -matrix interactions, but also has de-adhesive and growth inhibitory properties in non-transformed cells . In cancer, SPARC may exert divergent actions reflecting the complexity of this protein (Clark and Sage, 2008;Podhajcer et al, 2008). 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 .…”

mentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell -cell and cell -matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs. CONCLUSION: Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions.

show abstract

“…19 SPARC has been implicated in tissue remodeling during embryogenesis, wound healing, immune responses, 20 cancer stromatogenesis, and epithelial-to-mesenchymal transition. [19][20][21] In myeloid malignancies, SPARC (5q31. deletion has been associated with 5qϪ MDS, 22 and low or absent SPARC expression has been reported in a subset of AML.…”

Section: Introductionmentioning

confidence: 99%

Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion

Tripodo

Sangaletti

Guarnotta

et al. 2012

Blood

View full text Add to dashboard Cite

In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146 ؉ mesenchymal stromal cells, correlates with the degree of stromal changes, and the sever-

show abstract

A prototypic matricellular protein in the tumor microenvironment—Where there's SPARC, there's fire

Cited by 115 publications

References 100 publications

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

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

Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion

Contact Info

Product

Resources

About