The CCN family of genes: a perspective on CCN biology and therapeutic potential

Yeger, Herman; Perbal, Bernard

doi:10.1007/s12079-008-0022-6

Cited by 80 publications

(85 citation statements)

References 20 publications

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“…Of interest, the expression of genes of the WNT signaling pathway (Wnt10a, Sfrp1, Tcf4, Ccnd1) was upregulated in ATII cells during bleomycin-induced lung fibrosis. In particular, expression of Wisp1, a member of the recently described CCN family of secreted signaling molecules (21,22), was highly upregulated ( Figure 2B). …”

Section: Figurementioning

confidence: 94%

WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis

Königshoff¹,

Kramer²,

Balsara³

et al. 2009

J. Clin. Invest.

373

466

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Idiopathic pulmonary fibrosis (IPF) is characterized by distorted lung architecture and loss of respiratory function. Enhanced (myo)fibroblast activation, ECM deposition, and alveolar epithelial type II (ATII) cell dysfunction contribute to IPF pathogenesis. However, the molecular pathways linking ATII cell dysfunction with the development of fibrosis are poorly understood. Here, we demonstrate, in a mouse model of pulmonary fibrosis, increased proliferation and altered expression of components of the WNT/β-catenin signaling pathway in ATII cells. Further analysis revealed that expression of WNT1-inducible signaling protein-1 (WISP1), which is encoded by a WNT target gene, was increased in ATII cells in both a mouse model of pulmonary fibrosis and patients with IPF. Treatment of mouse primary ATII cells with recombinant WISP1 led to increased proliferation and epithelial-mesenchymal transition (EMT), while treatment of mouse and human lung fibroblasts with recombinant WISP1 enhanced deposition of ECM components. In the mouse model of pulmonary fibrosis, neutralizing mAbs specific for WISP1 reduced the expression of genes characteristic of fibrosis and reversed the expression of genes associated with EMT. More importantly, these changes in gene expression were associated with marked attenuation of lung fibrosis, including decreased collagen deposition and improved lung function and survival. Our study thus identifies WISP1 as a key regulator of ATII cell hyperplasia and plasticity as well as a potential therapeutic target for attenuation of pulmonary fibrosis.

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Section: Figurementioning

confidence: 94%

WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis

Königshoff¹,

Kramer²,

Balsara³

et al. 2009

J. Clin. Invest.

373

466

View full text Add to dashboard Cite

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“…However, overexpression has been shown in several epithelial and non-epithelial malignancies, but prognostic implications remain to be confirmed (78). In the only study in CC, Gardini et al found over-expression in 60% of tumours, demonstrating a significantly improved disease-free and overall survival in this group compared with lowexpressors.…”

Section: Ccn Proteinsmentioning

confidence: 99%

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, the United Kingdom incidence now exceeding 1000 cases per year. It is an aggresive malignancy typified by unresponsiveness to existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though postoperative disease recurrence is common, with 5-year survival rates following resection of less then 25%. Developments in molecular techniques and improved understanding of the basis of carcinogenesis in CC has led to examination of the role of biomarkers in predicting poor outcome. This systematic review examines published evidence relating to the prognostic significance of these molecular markers in CC. Of the molecular markers which have been investigated to date p53 mutation, cyclins, proliferation indices, mucins, CA19-9, CRP, and aneuploidy appear to hold significant potential as predictors of outcome in CC. These and other biomarkers may themselves represent novel therapeutic targets for CC.

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“…The CCN3/NOV proteins regulate melanocyte proliferation and their adherence to the basement membrane (CCN3/CYR3, cystein-rich angiogenic protein encoded from 1p22p31; NOV, nephroblatoma overexpressed gene at 8q24.1). The CCN nomenclature is published by the International CCN Society: http://ccnsociety.com; CCN 4, 5, 6 = WISP 1, 2, 3 (see above) (168,169). IL-1ß is a CCN3 inducer; it could suppress the growth of low-grade melanoma cells.…”

Section: Malignant Cell Fusionsmentioning

confidence: 99%