The C-Terminal Peptide of Connective Tissue Growth Factor Blocks the Full Molecule Binding to Tubular Epithelial Cell

Shi, Yujun; Wang, W.; Tu, Zhaoxu; Zhang, L.; Qiu, Jing; Li, Q.; Ye, F.; Li, Shenxin; Bu, Hong; Li, Y.

doi:10.1016/j.transproceed.2006.06.093

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…Previous studies have shown that the CT domain of the CTGF protein binds to a variety of members from the integrin family in different cell types [24][25][26][27]. In order to assess the potential therapeutic effect of recombinant CTGF, in vitro adhesion and in vivo peritoneal metastasis of MKN45 cells were tested in the presence of the CT domain of recombinant CTGF.…”

Section: Ctgf Is a Potential Therapeutic Target For The Inhibition Ofmentioning

confidence: 99%

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3β1-dependent adhesion

et al. 2014

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Background Connective tissue growth factor (CTGF) plays important roles in normal and pathological conditions. The aim of this study was to investigate the role of CTGF in peritoneal metastasis as well as the underlying mechanism in gastric cancer progression. Methods CTGF expression levels for wild-type and stable overexpression clones were determined by Western blotting and quantitative polymerase chain reaction (Q-PCR). Univariate and multivariate analyses, immunohistochemistry, and survival probability analyses were performed on gastric cancer patients. The extracellular matrix components involved in CTGF-regulated adhesion were determined. Recombinant CTGF was added to cells or coinoculated with gastric cancer cells into mice to evaluate its therapeutic potential.Results CTGF overexpression and treatment with the recombinant protein significantly inhibited cell adhesion. In vivo peritoneal metastasis demonstrated that CTGFstable transfectants markedly decreased the number and size of tumor nodules in the mesentery. Statistical analysis of gastric cancer patient data showed that patients expressing higher CTGF levels had earlier TNM staging and a higher survival probability after the surgery. Integrin a3b1 was the cell adhesion molecule mediating gastric cancer cell adhesion to laminin, and blocking of integrin a3b1 prevented gastric cancer cell adhesion to recombinant CTGF. Coimmunoprecipitation results indicated that CTGF binds to integrin a3. Coinoculation of recombinant CTGF and gastric cancer cell lines in mice showed effective inhibition of peritoneal dissemination. Conclusions Our results suggested that gastric cancer peritoneal metastasis is mediated through integrin a3b1 binding to laminin, and CTGF effectively blocks the interaction by binding to integrin a3b1, thus demonstrating the therapeutic potential of recombinant CTGF in gastric cancer patients.

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Section: Ctgf Is a Potential Therapeutic Target For The Inhibition Ofmentioning

confidence: 99%

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3β1-dependent adhesion

et al. 2014

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The complex world of oligodendroglial differentiation inhibitors

Kremer

Aktaş

Hartung

et al. 2011

Annals of Neurology

121

101

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Myelination is a central nervous system (CNS) process wherein oligodendrocyte-axon interactions lead to the establishment of myelin sheaths that stabilize, protect, and electrically insulate axons. In inflammatory demyelinating diseases such as multiple sclerosis (MS), the degeneration and eventual loss of functional myelin sheaths slows and blocks saltatory conduction in axons, which results in clinical impairment. However, remyelination can occur, and lesions can be partially repaired, resulting in clinical remission. The recruitment and activation of resident oligodendrocyte precursor cells (OPCs) play a critical role in the repair process because these cells have the capacity to differentiate into functional myelinating cells. Mature oligodendrocytes, however, are thought to have lost the capacity to develop new myelin sheaths and frequently undergo programmed cell death in MS. The endogenous capacity to generate new oligodendrocytes in MS is limited, and this is predominantly due to the presence of inhibitory components that block OPC differentiation and maturation. Here, we present an overview of recently identified negative regulators of oligodendroglial differentiation and their potential relevance for CNS repair in MS. Because currently available immunomodulatory drugs for MS mainly target inflammatory cascades outside the brain and fail to repair existing lesions, achieving more efficient lesion repair constitutes an important goal for future MS therapies.

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Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

Guillon-Munos

Οικονομοπούλου

Michel

et al. 2011

Journal of Biological Chemistry

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Kallikrein-related peptidases (KLKs) are an emerging group of secreted serine proteases involved in several physiological and pathological processes. We used a degradomic approach to identify potential substrates of KLK12. MDA-MB-231 cells were treated either with KLK12 or vehicle control, and the proteome of the overlying medium was analyzed by mass spectrometry. CCN1 (cyr61, ctgf, nov) was among the proteins released by the KLK12-treated cells, suggesting that KLK12 might be responsible for the shedding of this protein from the cell surface. Fragmentation of CCN1 by KLK12 was further confirmed in vitro, and the main cleavage site was localized in the hinge region between the first and second half of the recombinant protein. KLK12 can target all six members of the CCN family at different proteolytic sites. Limited proteolysis of CCNs (cyr61, ctgf, nov) was also observed in the presence of other members of the KLK family, such as KLK1, KLK5, and KLK14, whereas KLK6, KLK11, and KLK13 were unable to fragment CCNs. Because KLK12 seems to have a role in angiogenesis, we investigated the relations between KLK12, CCNs, and several factors known to be involved in angiogenesis. Solid phase binding assays showed that fragmentation of CCN1 or CCN5 by KLK12 prevents VEGF 165 binding, whereas it also triggers the release of intact VEGF and BMP2 from the CCN complexes. The KLK12-mediated release of TGF-␤1 and FGF-2, either as intact or truncated forms, was found to be concentration-dependent. These findings suggest that KLK12 may indirectly regulate the bioavailability and activity of several growth factors through processing of their CCN binding partners.

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The C-Terminal Peptide of Connective Tissue Growth Factor Blocks the Full Molecule Binding to Tubular Epithelial Cell

Cited by 4 publications

References 14 publications

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3β1-dependent adhesion

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3β1-dependent adhesion

The complex world of oligodendroglial differentiation inhibitors

Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

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