Coexpressed High Levels of VEGF-C and Active MMP-9 Are Associated With Lymphatic Spreading and Local Invasiveness of Papillary Thyroid Carcinoma

Šelemetjev, Sonja; Đorić, Ilona; Paunović, Ivan; Tatic, Svetislav; Cvejić, Dubravka

doi:10.1093/ajcp/aqw184

Cited by 26 publications

(24 citation statements)

References 30 publications

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“…LN metastasis is a complex multistep process (30). In addition to intratumoral and peritumoral lymphangiogenesis, enhanced cell invasion and extracellular matrix degradation are essential for metastasis (31,32). Importantly, we noticed that the tumors formed by the BLACAT2-transduced bladder cancer cells grown in the footpads of the nude mice displayed spike-like structures that invaded the surrounding be involved in the EMT of bladder cancer cells.…”

Section: Blacat2 Induces Lymphangiogenesis In Vivo and In Vitromentioning

confidence: 87%

“…Accumulating evidence has been provided that VEGF-C signaling, which plays critical roles in lymphangiogenesis and LN metastasis, may serve as a potential therapeutic target for LN-metastatic cancer (32,34,40,41). We tested to determine whether downregulation of VEGF-C could inhibit BLACAT2-induced LN metastasis.…”

Section: Vegf-c Is Required For Blacat2-induced Lymphangiogenesis Andmentioning

confidence: 99%

See 1 more Smart Citation

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Wang¹,

Zhong²,

Jiang³

et al. 2018

Journal of Clinical Investigation

160

151

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Section: Blacat2 Induces Lymphangiogenesis In Vivo and In Vitromentioning

confidence: 87%

Section: Vegf-c Is Required For Blacat2-induced Lymphangiogenesis Andmentioning

confidence: 99%

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Wang¹,

Zhong²,

Jiang³

et al. 2018

Journal of Clinical Investigation

160

151

View full text Add to dashboard Cite

“…LN metastasis is a complex multistep process. In addition to intratumoral and peritumoral lymphangiogenesis in vivo, enhanced cell migration and invasion is essential for metastasis 31 , 32 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment

et al. 2018

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Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1-modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer.

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“…LN metastasis is a complex multistep process [ 6 ]. In addition to intratumoral and peritumoral lymphangiogenesis, enhanced cell invasion and migration are essential for metastasis [ 37 , 38 ]. As described above, miR-548k overexpression promoted cell mobility and invasiveness (Additional file 2 : Figure S1f, g).…”

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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Coexpressed High Levels of VEGF-C and Active MMP-9 Are Associated With Lymphatic Spreading and Local Invasiveness of Papillary Thyroid Carcinoma

Abstract: Association of coexpressed high levels of VEGF-C and active MMP-9 with lymphatic spreading and local invasiveness of PTC suggests their potential usefulness as predictive biomarkers of aggressive PTC behavior.

Cited by 26 publications

References 30 publications

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment

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

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