Modulation of matrix remodeling by SPARC in neoplastic progression

Chlenski, Alexandre; Cohn, Susan L.

doi:10.1016/j.semcdb.2009.11.018

Cited by 134 publications

(120 citation statements)

References 132 publications

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“…Based on these selection criteria, we selected SPARC. SPARC/Osteonectin is a matrix-associated protein that elicits changes in cell shape, inhibits cell-cycle progression and influences the synthesis of extracellular matrix (ECM) (Brekken and Sage, 2001;Chlenski and Cohn, 2010). Moreover, SPARC was a good candidate to explain the in vivo DN_IRE1 expressing tumor phenotype previously observed.…”

Section: Ire1a Signaling Regulates Migration Of U87 Cells By Downregumentioning

confidence: 98%

Autocrine control of glioma cells adhesion/migration through Inositol Requiring enzyme 1α (IRE1α)-mediated cleavage of Secreted Protein Acidic Rich in Cysteine (SPARC) mRNA

Dejeans

Pluquet

Lhomond

et al. 2012

Journal of Cell Science

101

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SummaryThe endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory and transmembrane proteins. ER homeostasis is often perturbed in tumor cells because of dramatic changes in the microenvironment of solid tumors, thereby leading to the activation of an adaptive mechanism named the unfolded protein response (UPR). The activation of the UPR sensor IRE1a has been described to play an important role in tumor progression. However, the molecular events associated with this phenotype remain poorly characterized. In the present study, we examined the effects of IRE1a signaling on the adaptation of glioma cells to their microenvironment. We show that the characteristics of U87 cell migration are modified under conditions where IRE1a activity is impaired (DN_IRE1). This is linked to increased stress fiber formation and enhanced RhoA activity. Gene expression profiling also revealed that loss of functional IRE1a signaling mostly resulted in the upregulation of genes encoding extracellular matrix proteins. Among these genes, Sparc, whose mRNA is a direct target of IRE1a endoribonuclease activity, was in part responsible for the phenotypic changes associated with IRE1a inactivation. Hence, our data demonstrate that IRE1a is a key regulator of SPARC expression in vitro in a glioma model. Our results also further support the crucial contribution of IRE1a to tumor growth, infiltration and invasion and extend the paradigm of secretome control in tumor microenvironment conditioning.

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Section: Ire1a Signaling Regulates Migration Of U87 Cells By Downregumentioning

confidence: 98%

Autocrine control of glioma cells adhesion/migration through Inositol Requiring enzyme 1α (IRE1α)-mediated cleavage of Secreted Protein Acidic Rich in Cysteine (SPARC) mRNA

Dejeans

Pluquet

Lhomond

et al. 2012

Journal of Cell Science

101

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“…[7][8][9][10]. Interest in SPARC has grown in recent years because of its apparent role in regulating tumor growth via its production by both cancer and or stromal cells and based on its interactions with biologically active cytokines/chemokines in the tumor milieu (summarized in refs.…”

Section: Introductionmentioning

confidence: 99%

Loss of SPARC in bladder cancer enhances carcinogenesis and progression

Said¹,

Frierson²,

Sänchez‐Carbayo³

et al. 2013

J. Clin. Invest.

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Secreted protein acidic and rich in cysteine (SPARC) has been implicated in multiple aspects of human cancer. However, its role in bladder carcinogenesis and metastasis are unclear,with some studies suggesting it may be a promoter and others arguing the opposite. Using a chemical carcinogenesis model in Sparc-deficient mice and their wild-type littermates, we found that loss of SPARC accelerated the development of urothelial preneoplasia (atypia and dysplasia), neoplasia, and metastasis and was associated with decreased survival. SPARC reduced carcinogen-induced inflammation and accumulation of reactive oxygen species as well as urothelial cell proliferation. Loss of SPARC was associated with an inflammatory phenotype of tumor-associated macrophages and fibroblasts, with concomitant increased activation of urothelial and stromal NF-κB and AP1 in vivo and in vitro. Syngeneic spontaneous and experimental metastasis models revealed that tumorand stroma-derived SPARC reduced tumor growth and metastasis through inhibition of cancer-associated inflammation and lung colonization. In human bladder tumor tissues, the frequency and intensity of SPARC expression were inversely correlated with disease-specific survival. These results indicate that SPARC is produced by benign and malignant compartments of bladder carcinomas where it functions to suppress bladder carcinogenesis, progression, and metastasis.

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“…SPARC mediates to interactions between cell and its surrounding environment by fusing with collagen, laminin, fibronectin and vitronectin (Podhajcer et al, 2008;Huang et al, 2010). SPARC regulates many biological processes such as cell proliferation and survival, apoptosis, adhesion or migration (Tai et al, 2008;Chlenski et al, 2010). In normal tissues, the SPARC expression is limited to intestinal epithelium, osseous epithelium and tissues undergoing remodeling or repairing (Chin et al, 2005).…”

Section: Introductionmentioning

confidence: 99%