Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation

Enomoto, Hiroyuki; Nelson, Courtney M.; Somerville, Robert; Mielke, Katrina; Dixon, Laura; Powell, Kimerly; Apte, Suneel S.

doi:10.1242/dev.050591

Cited by 129 publications

(153 citation statements)

References 56 publications

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“…23 Cleavage of versican by ADAMTS proteases is a context-dependent morphogenic signal, 25,26 and N-terminal (G1) and C-terminal (G3) versican fragments enhance tumor growth, invasiveness, and metastasis. 48,50 -53 The local accumulation of versican fragments generated by ADAMTS1 digestion may promote cancer cell motility and invasion.…”

Section: Discussionmentioning

confidence: 99%

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Ricciardelli

Frewin

Tan

et al. 2011

The American Journal of Pathology

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The A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of proteins is composed of extracellular metalloproteases, including ADAMTS1, originally identified in cachexigenic colon cancer cells. 1,2 Mice with Adamts1-null mutation exhibit urogenital defects and female infertility because of impaired remodeling of ovarian extracellular matrix (ECM), but ovarian steroid production and lactation are normal. 3-5 A range of ECM proteins have been identified as potential ADAMTS1 substrates, including collagens, 6 nidogen, 7 and syndecan-4 8 ; however, the proteoglycans versican and aggrecan have been consistently shown to be key ADAMTS1 targets. 4,9,10 ADAMTS1 processing of versican is important in cell migration during wound healing, 11 endothelial cell invasion, 12 and remodeling of cardiac jelly ECM during heart morphogenesis. 13 These observations indicate that ADAMTS1 mediates acute regulated tissue remodeling processes that occur in development and in adult reproductive tissues, but also in cancer growth and metastasis.Emerging evidence associates ADAMTS1 expression with metastatic potential. Elevated expression of ADAMTS1 is characteristic of breast cancer cell lines 14,15 and human breast cancers with high bone metastatic potential. 16 Likewise, local invasion and lymph node metastasis of pancreatic cancer is associated with elevated Adamts1. 17 Overexpression of full-length ADAMTS1 in

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Section: Discussionmentioning

confidence: 99%

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Ricciardelli

Frewin

Tan

et al. 2011

The American Journal of Pathology

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“…Proteolytic processing of versican is essential in a number of developmental processes and generates bioactive fragments including G1-DPEAAE 441 . [63][64][65][66][67][68] It is becoming increasingly clear that the regulated expression and proteolytic processing of versican are critically involved in influencing cell phenotype during inflammation and remodeling. 51,69 Bioactive ECM proteolytic fragments are increasingly recognized to regulate cellular function and have been generally referred to as matrikines.…”

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confidence: 99%

Versican: a novel modulator of hepatic fibrosis

Bukong

Maurice

Chahal

et al. 2016

Laboratory Investigation

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Little is known about the deposition and turnover of proteoglycans in liver fibrosis, despite their abundance in the extracellular matrix. Versican plays diverse roles in modulating cell behavior in other fibroproliferative diseases, but remains poorly described in the liver. Hepatic fibrosis was induced by carbon tetrachloride treatment of C57BL/6 mice over 4 weeks followed by recovery over a 28-day period. Primary mouse hepatic stellate cells (HSCs) were activated in culture and versican was transiently knocked down in human (LX2) and mouse HSCs. Expression of versican, A Disintegrinlike and Metalloproteinase with Thrombospondin-1 motifs (ADAMTS)-1, -4, -5, -8, -9, -15, and -20, and markers of fibrogenesis were studied using immunohistochemistry, real-time quantitative PCR, and western blotting. Immunohistochemistry showed increased expression of versican in cirrhotic human livers and the mouse model of fibrosis. Carbon tetrachloride treatment led to significant increases in versican expression and the proteoglycanases ADAMTS-5, -9, -15, and -20, alongside TNF-α, α-smooth muscle actin (α-SMA), collagen-1, and TGF-β expression. During recovery, expression of many of these genes returned to control levels. However, expression of ADAMTS-5, -8, -9, and -15 showed delayed increases in expression at 28 days of recovery, which corresponded with decreases in versican V0 and V1 cleavage products (G1-DPEAAE 1401 and G1-DPEAAE 441 ). Activation of primary HSCs in vitro significantly increased versican, α-SMA, and collagen-1 expression. Transient knockdown of versican in HSCs led to decreases in markers of fibrogenesis and reduced cell proliferation, without inducing apoptosis. Versican expression increases during HSC activation and liver fibrosis, and proteolytic processing occurs during the resolution of fibrosis. Knockdown studies in vitro suggest a possible role of versican in modulating hepatic fibrogenesis.

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“…43 ADAMTS9 and -20 also belong to aggrecanases and degrade versican and aggrecan in ECM. 44 ADAMTS20 is over-expressed in brain, colon and breast carcinomas. 41 In our study, ADAMTS20 has increased just after insulin application, but after that, it has decreased in day 3 and protected its low level throughout the study interval.…”

Section: Discussionmentioning

confidence: 99%

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

Işık¹

2015

UHOD

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Some of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes have been suggested to facilitate invasion and metastasis in cancer. ADAMTS20 is called gon-ADAMTS and ADAMTS10 and -17 are called orphan ADAMTSs. ADAMTS20 degrades versican and aggrecan in extracellular matrix. We aimed to investigate the effects of insulin on ADAMTS10,-17 and -20 in OUMS-27 chondrosarcoma cells. OUMS-27 cells were cultured in Dulbecco's modified Eagle' medium (DMEM) containing 10 μg/mL insulin. The medium was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and RNA isolation was performed at appropriate times according to study setup. The levels of RNA expression of ADAMTS10,-17 and -20 were estimated by qRT-PCR using appropriate primers. ADAMTS10 mRNA expression gradually decreased within 7 days after insulin induction compared to control group. There was a significant difference between control and Day 7 groups (p=0.021) as well as Day 1 and Day 7 groups (p=0.028). ADAMTS17 mRNA expression increased right after insulin induction at day 1 compared to control group and protected its high levels throughout insulin application. The most evident and statistically significant increase in mRNA concentration was observed at day 7 after insulin induction (p= 0.014). Our results demonstrated that ADAMTS10,-17 and -20 might have a role in cancer progression. Although functions of ADAMTS10 and -17 are not known, their expression levels have changed in chondrosarcoma cell line. Further studies are needed to characterize chondrosarcoma cells because of the possible association between cancer progression and ADAMTS proteins. Keywords: ADAMTS, Chondrosarcoma, Insulin, qRT-PCR, OUMS-27 ÖZET Kondrosarkom Hücrelerinde Orfan ve gon-ADAMTS'ların Ekspresyonundaki DeğişimlerA disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzimlerinden bazılarının kanserde invazyon ve metastazı kolaylaştıracağı öngörülmektedir. ADAMTS20, gon-ADAMTS olarak ve ADAMTS10 ile -17, orfan ADAMTS olarak adlandırılır. Bunlardan ADAMTS20 hücre dışı matrikste versikan ve agrekanı parçalayan enzim olarak bilinir. Bu çalışmada OUMS-27 hücrelerinde insülinin ADAMTS10, -17 ve -20 üzerine etkilerinin araştırılması amaçlandı. OUMS-27 hücreleri 10 μg/ml insülin içeren Dulbecco's Modified Eagle Medium (DMEM) ortamında kültüre edildiler. Medyum 11. güne kadar iki günde bir değiştirildi. Hücreler 1, 3, 7 ve 11. günlerde toplandı ve her birinde aynı gün RNA izolasyonları gerçekleştirildi. ADAMTS10, -17 ve -20'nin RNA ekspresyon düzeyleri uygun primerler kullanılarak qRT-PCR ile hesaplandı. Kontrol grubuyla karşılaştırıldığında, ADAMTS10 mRNA ekspresyonu insülin indüksiyonundan sonra 7 gün içinde gittikçe azalmıştır. Kontrol ile 7. gün grubu arasında (p=0.021) ve 1. gün ve 7. gün grubu (p=0.028) arasında anlamlı farklılıklar vardı. Kontrol grubuyla karşılaştırıldığında ADAMTS17 mRNA ekspresyonu insülin indüksiyonundan hemen sonra 1. günde yükselmiş ve yüksek seviyelerini insülin uygulaması boyunca k...

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Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation

Cited by 129 publications

References 56 publications

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Versican: a novel modulator of hepatic fibrosis

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

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