ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

Inagaki, Jiro; Takahashi, Katsuyuki; Ogawa, Hiroyasu; Asano, Keiichi; Hatipoğlu, Ömer Faruk; Cilek, Mehmet Zeynel; Obika, Masanari; Ohtsuki, Takashi; Hofmann, Matthias; Kusachi, Shozo; Ninomiya, Yoshifumi; Hirohata, Satoshi

doi:10.1016/j.yexcr.2014.03.002

Cited by 20 publications

(13 citation statements)

References 49 publications

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“…However, MMP-19, which is up-regulated in various cancer tissues, facilitates tumor invasion [ 25 ]. Consistent with the anti-angiogenic efficacy of MMP19, several reports have demonstrated that metallopeptidase with thrombospondin type-1 motif (ADAMTS1), which was up-regulated in MALAT-1-silencing cells to inhibit angiogenesis [ 26 – 28 ] , and decreased ADAMTS1 stimulated migration and invasion of breast cancer cells [ 29 ].…”

Section: Discussionmentioning

confidence: 90%

The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

Zhou

et al. 2016

PLoS ONE

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BackgroundMetastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.MethodsExpressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.ResultsWe found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.ConclusionsThe present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.

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Section: Discussionmentioning

confidence: 90%

The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

Zhou

et al. 2016

PLoS ONE

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“…According to gene ontology annotation, we selected ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) for further study. Given that ADAMTS1 was implicated in lymphangiogensis [ 40 ], we hypothesized miR-548k regulating the lymphatic metastasis through targeting ADAMTS1. Our analysis revealed that the 3’-UTR of ADAMTS1 mRNA contains a complementary site for the seed region of miR-548k, which is conservative across different species (Fig.…”

Section: Resultsmentioning

confidence: 99%

The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment

Zhang

Hong

et al. 2018

Mol Cancer

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BackgroundThe prognosis for esophageal squamous cell carcinoma (ESCC) patients with lymph node metastasis (LNM) is still dismal. Elucidation of the LNM associated genomic alteration and underlying molecular mechanisms may provide clinical therapeutic strategies for ESCC treatment.MethodsJoint analysis of ESCC sequencing data were conducted to comprehensively survey SCNAs and identify driver genes which significantly associated with LNM. The roles of miR-548k in lymphangiogensis and lymphatic metastasis were validated both in vitro and in vivo. ESCC tissue and blood samples were analyzed for association between miR-548k expression and patient clinicopathological features and prognosis and diagnosis.ResultsIn the pooled cohort of 314 ESCC patients, we found 76 significant focused regions including 43 amplifications and 33 deletions. Clinical implication analysis revealed a panel of genes associated with LNM with the most frequently amplified gene being MIR548K harbored in the 11q13.3 amplicon. Overexpression of miR-548k remarkably promotes lymphangiogenesis and lymphatic metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-548k modulating the tumor microenvironment by promoting VEGFC secretion and stimulating lymphangiogenesis through ADAMTS1/VEGFC/VEGFR3 pathways, while promoting metastasis by regulating KLF10/EGFR axis. Importantly, we found that serum miR-548k and VEGFC of early stage ESCC patients were significantly higher than that in healthy donators, suggesting a promising application of miR-548k and VEGFC as biomarkers in early diagnosis of ESCC.ConclusionsOur study comprehensively characterized SCNAs in ESCC and highlighted the crucial role of miR-548k in promoting lymphatic metastasis, which might be employed as a new diagnostic and prognostic marker for ESCC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0871-4) contains supplementary material, which is available to authorized users.

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“…TaqMan primers and probes (human ADAMTS4: assay ID Hs00192708_m1 based on RefSeq NM_005099.4; human ADAMTS5: assay ID Hs00199841_m1 based on RefSeq NM_007038.3; human ADAMTS9: assay ID Hs00172025_m1 based on RefSeq NM_182920.1; human MMP‐13: assay ID Hs00233992_m1 based on RefSeq NM_002427.3; human GAPDH: assay ID Hs02758991_g1 based on RefSeq NM_001256799.1 and NM_002046.4; rat ADAMTS4: assay ID Rn02103282_s1 based on RefSeq NM_023959.1; rat ADAMTS5: Rn01458486_m1 based on RefSeq NM_198761.1; rat ADAMTS9: Rn01425216_m1 RefSeq NM_001107877.1; rat GAPDH: Rn01462662_g1 RefSeq NM_017008.4) and TaqMan Fast Advanced Master Mix were purchased from Applied Biosystems. GAPDH was used to normalize the levels of target RNA with the comparative Ct (ΔΔCT) method as previously described . Values obtained from untreated cells were considered as controls.…”

Section: Methodsmentioning

confidence: 99%

High molecular weight hyaluronan protects cartilage from degradation by inhibiting aggrecanase expression

Ohtsuki

Asano

Inagaki

et al. 2018

Journal Orthopaedic Research

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Hyaluronan (HA) is an extracellular matrix (ECM) component of articular cartilage and has been used to treat patients with osteoarthritis (OA). A disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs) play an important role in cartilage degradation in OA. We have previously reported that ADAMTS4 and ADAMTS9 were induced by cytokine stimulation. However, the effect of HA on the cytokine-inducible ADAMTS9 has never been investigated. Moreover, it is unclear whether HA protects cartilage by suppressing aggrecan degradation. Here, we examined the effects of HA on ADAMTS expression in vitro and on cartilage degradation in vivo. ADAMTS9 expression was higher than that of the other aggrecanases (ADAMTS4 and 5) in human chondrocytes, chondrocytic cells, and rat cartilage. ADAMTS4 and 9 mRNA levels were upregulated in cytokine-stimulated chondrocytes and chondrocytic cells. Pre-incubation with HA significantly inhibited ADAMTS9 mRNA expression in cytokine-stimulated cells. In a rat OA model, Adamts5 and 9 mRNA levels were transiently increased after surgery; intra-articular HA injections attenuated the induction of Adamts5 and 9 mRNA. HA also blocked aggrecan cleavage by aggrecanase in OA rats in a molecular size-dependent manner. These results demonstrate that HA attenuates induced aggrecanases expression in OA and thereby protects articular cartilage degradation by this enzyme. Our findings provide insight into the molecular basis for the beneficial effects of HA in OA. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 9999:1-9, 2018.

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ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

Cited by 20 publications

References 49 publications

The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment

High molecular weight hyaluronan protects cartilage from degradation by inhibiting aggrecanase expression

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