Human CYR61-mediated enhancement of bFGF-induced DNA synthesis in human umbilical vein endothelial cells

Kolesnikova, Tatiana V.; Lau, Lester F.

doi:10.1038/sj.onc.1201572

Cited by 71 publications

(67 citation statements)

References 20 publications

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“…Therefore, Cyr61 protein expression seems to be associated with hypertrophic and rapidly proliferating smooth muscle cells, as 50-90% of the cells in the obstructed bladders consist of hypertrophic/hyperplastic smooth muscle cells (1,55). However, in vitro studies have shown that the purified Cyr61 does not have intrinsic mitogenic activity but enhances growth factor-induced cell proliferation in both fibroblast and endothelial cells (29). It was proposed that Cyr61 action becomes most relevant when the concentration of growth factors in the immediate cell microenvironment is limiting.…”

Section: Discussionmentioning

confidence: 99%

Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction

Chaqour

Whitbeck

Han

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Cysteine-rich protein (Cyr61) and connective tissue growth factor (CTGF) are key immediate early growth factors with functions in cell proliferation, differentiation, and extracellular matrix synthesis. Studies were performed to assess the gene expression profile of Cyr61 and CTGF in rat urinary bladder during growth in response to partial outlet obstruction. The mRNA levels of Cyr61 as determined by ribonuclease protection assay increased sharply after 1 day and remained elevated throughout the time period of the obstruction. This correlates well with increased bladder weight. The CTGF mRNA levels seemed to peak within the second week of the urethral obstruction and correlate well with increased type I collagen mRNA. The expression pattern of either Cyr61 or CTGF proteins corroborated that of their respective mRNAs. Immunohistochemical analyses showed that immunoreactivity of Cyr61 was confined to detrusor smooth muscle and that of CTGF was detected within both detrusor muscle and lamina propria layers. These data strongly indicate the involvement of Cyr61 and CTGF in bladder wall remodeling as a result of the outlet obstruction.

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Section: Discussionmentioning

confidence: 99%

Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction

Chaqour

Whitbeck

Han

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…An alternative explanation of our findings would be that intact CCN1 and CCN5 act as cofactors to potentiate VEGF 165 effects on VEGFR2 signaling. As a proof of principle, CCNs have already been described to potentiate the activities of TGF-␤1, FGF-2, and BMP2 (32,(35)(36).…”

Section: Discussionmentioning

confidence: 99%

“…It has been previously shown that CCN1 enhances FGF-2-induced DNA synthesis in HUVECs likely because of FGF-2 displacement from extracellular matrix (36). To determine C and D, CCN1 or CCN5 complexes with VEGF were formed by incubation for 12 h at 4°C and then incubated with KLK12 for 3 h at 37°C.…”

Section: Klk12 Processing Of Ccn1 or Ccn5 Complexes Mobilizesmentioning

confidence: 99%

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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“…It has attracted considerable interest in cancer research because of its regulatory functions in several processes relevant in tumor biology including cell adhesion, migration, proliferation, differentiation, angiogenesis, apoptosis, and survival. (11)(12)(13)(14)(15)(16) In breast cancer, Cyr61 was found to be expressed at higher levels in tumors than in normal breast tissue, and increased expression correlated with tumor size, involvement of lymph nodes, and metastatic potential of tumor cells and consequently poor survival. (17)(18)(19) In glioma, Cyr61 was found overexpressed in primary tumors compared with normal tissue, and its expression levels correlated significantly with tumor grade and inversely with patient survival.…”

Section: J Jbmrmentioning

confidence: 99%

Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice

Sabile

Arlt

Muff

et al. 2011

Journal of Bone and Mineral Research

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Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents with a high propensity for lung metastasis, the major cause of disease-related death. Reliable outcome-predictive markers and targets for osteosarcoma metastasissuppressing drugs are urgently needed for more effective treatment of metastasizing osteosarcoma, which has a current mean 5-year survival rate of approximately 20%. This study investigated the prognostic value and the biological relevance of the extracellular matrixassociated growth factor Cyr61 of the CCN family of secreted proteins in osteosarcoma and metastasis. The prognostic value of Cyr61 was assessed with Kaplan-Meier analyses based on Cyr61 immunostaining of a tissue microarray of osteosarcoma biopsies collected from 60 patients with local or metastatic disease. Effects of Cyr61 overexpression on intratibial tumor growth and lung metastasis of the low metastatic human SaOS-2 osteosarcoma cell line were examined in severe combined immunodeficiency (SCID) mice. Cyr61-provoked signaling was studied in vitro in nonmanipulated SaOS-2 cells. Cyr61 immunostaining of osteosarcoma tissue cores correlated significantly (p ¼ 0.02) with poor patient survival. Mice intratibially injected with Cyr61-overexpressing SaOS-2 cells showed faster tumor growth and an increase in number and outgrowth of lung metastases and consequently significantly (p ¼ 0.0018) shorter survival than mice injected with control SaOS-2 cells. Cyr61-evoked PI-3K/Akt/GSK3b signaling in SaOS-2 cells resulted in a subcellular redistribution of the cell cycle inhibitor p21 Cip1/WAF1 . Cyr61 has considerable potential as a novel marker for poor prognosis in osteosarcoma and is an attractive target for primary tumor-and metastases-suppressing drugs. ß

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Human CYR61-mediated enhancement of bFGF-induced DNA synthesis in human umbilical vein endothelial cells

Cited by 71 publications

References 20 publications

Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction

Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction

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

Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice

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