The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

Tan, Izza de Arao; Ricciardelli, Carmela; Russell, Darryl L.

doi:10.1002/ijc.28127

Cited by 66 publications

(44 citation statements)

References 159 publications

(311 reference statements)

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“…ADAMTS-1 cleaves the proteoglycans aggrecan and versican and has been shown to have a potential collagenase activity [60,61]. ADAMTS-1 also participates in stromal activation and has been shown to be upregulated by IL1β and downregulated by TGFβ in decidual stromal cells [62,63].…”

Section: Discussionmentioning

confidence: 99%

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

Bras

Taylor

Koumangoye

et al. 2015

Experimental Cell Research

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The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83–01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83–01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion.

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Section: Discussionmentioning

confidence: 99%

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

Bras

Taylor

Koumangoye

et al. 2015

Experimental Cell Research

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“…There are few contributions on ADAMTS in ovarian cancer in the literature. According to de Arao Tan et al [9], ADAMTS-1 is downregulated in ovarian cancer compared to normal tissue. Overexpression of the ADAMTS-1 C-terminal fragment DPM-1 in CHO cells induced tumors with a marked decrease in metastatic activity in nude mice.…”

Section: Discussionmentioning

confidence: 99%

“…They share homology in the catalytic ADAM metalloprotease and disintegrin domains, but they differ in variable numbers of thrombospondin-like motifs and other carboxyl-terminal domains associated with ECM interaction [6,8,9]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer

Lima¹,

Santos²,

Turri³

et al. 2016

Pathobiology

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Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.

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“…Some of them has been investigated for their role in cancer development, angiogenesis, and metastatic progression. 25,26 This is the first study in the literature on expression levels of orphan and gon-ADAMTS in insulin-induced human chondrosarcoma cell line. Also, there have been no studies about the levels of ADAMTS proteinases (ADAMTS10, -17 and -20) in chondrosarcoma cells in literature so far.…”

Section: Discussionmentioning

confidence: 98%

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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The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

Cited by 66 publications

References 159 publications

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer

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

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