The tripeptide-copper complex glycyl-L-histidyl-L- lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures

Siméon, Alain; Emonard, Hervé; Hornebeck, William; Maquart, François‐Xavier

doi:10.1016/s0024-3205(00)00803-1

Cited by 94 publications

(67 citation statements)

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“…The negative enhancement was consistently achieved at low dosage in several different cell lines demonstrating their robustness in vitro. NHK is a potent wound healing agent and activator of extracellular matrix (ECM) synthesis and remodelling [22,23]; securinine is a novel immune cell agonist [24,25]. The identification of these two perturbagens from a host of 1,309 active bio-molecules indicates that the wound healing and Rank refers to the order of the instance in the query; the instances are ranked according to the connectivity score in descending order from ?1 to -1.…”

Section: Discussionmentioning

confidence: 99%

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

Hong

Downey

et al. 2010

Clin Exp Metastasis

287

208

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Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 x 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the ;Connectivity Map' with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.

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Section: Discussionmentioning

confidence: 99%

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

Hong

Downey

et al. 2010

Clin Exp Metastasis

287

208

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“…In addition, it has been shown that copper is required as a cofactor for many key mediators of angiogenesis, such as basic fibroblast growth factor (FGF) matrix metalloproteinase, and angiogenin (17)(18)(19)(20). Several clinical trials have been carried out in recent years to evaluate the antiangiogenic effects of copper chelators on solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular Carcinoma Associated with Wilson's Disease

et al. 2004

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A 23-year-old man was admitted to our department due to hemorrhage from gastric varices. He had been diagnosed as having Wilson's disease at the age of 17. Abdominal ultrasonography and computed tomography (CT) showed portal thrombosis and a large mass occupying most of the right lobe in the liver. The tumor was diagnosed as hepatocellular carcinoma (HCC) by image views and tumor markers. He died 3 months after the diagnosis, and an autopsy was performed. Histologic examination of the tumor showed moderately to poorly differentiated HCC. The nontumorous lesion of the liver revealed cirrhosis. HBX-DNA sequence was not detected in the liver. Hepatic cirrhosis is a well-recognized complication of Wilson's disease, but HCC is extremely rare. We describe the clinical findings of this patient and discuss the relationship of the development of HCC with a review of the relevant literature.

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“…Although SPARC, acting as a pleiotropic factor during angiogenesis, suppresses vascular growth through the inhibition of VEGF-dependent pathways [66,67], its proteolytic cleavage occurring at wound sites causes the release of copper-binding peptides containing the sequence GHK-Cu 2+ (glycyl-histidyl-lysine), which potently stimulate wound healing [68,69]. The naturally occurring serum GHK-Cu 2+ tripeptide complex enhances the growth of blood vessels by modulating ECM remodelling through the synthesis and accumulation of matrix components, including glycosaminoglycans and small proteoglycans [70], and stimulating the MMP-2 (matrix metallo-proteinase 2) activity [71]. However, GHK-Cu 2+ targets are not limited to ECM components.…”

Section: Copper Tunes the Activity Of Several Pro-angiogenic Factorsmentioning

confidence: 99%

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

Urso

Maffia²

2015

J Vasc Res

129

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Angiogenesis critically sustains the progression of both physiological and pathological processes. Copper behaves as an obligatory co-factor throughout the angiogenic signalling cascades, so much so that a deficiency causes neovascularization to abate. Moreover, the progress of several angiogenic pathologies (e.g. diabetes, cardiac hypertrophy and ischaemia) can be tracked by measuring serum copper levels, which are being increasingly investigated as a useful prognostic marker. Accordingly, the therapeutic modulation of body copper has been proven effective in rescuing the pathological angiogenic dysfunctions underlying several disease states. Vascular copper transport systems profoundly influence the activation and execution of angiogenesis, acting as multi-functional regulators of apparently discrete pro-angiogenic pathways. This review concerns the complex relationship among copper-dependent angiogenic factors, copper transporters and common pathological conditions, with an unusual accent on the multi-faceted involvement of the proteins handling vascular copper. Functions regulated by the major copper transport proteins (CTR1 importer, ATP7A efflux pump and metallo-chaperones) include the modulation of endothelial migration and vascular superoxide, known to activate angiogenesis within a narrow concentration range. The potential contribution of prion protein, a controversial regulator of copper homeostasis, is discussed, even though its angiogenic involvement seems to be mainly associated with the modulation of endothelial motility and permeability.

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The tripeptide-copper complex glycyl-L-histidyl-L- lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures

Cited by 94 publications

References 0 publications

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

Hepatocellular Carcinoma Associated with Wilson's Disease

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

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