Influence of lymphatic endothelial cells on proliferation and invasiveness of esophageal carcinoma cells in vitro and lymphangiogenesis in vivo

Xu, Yang; Nana, Zhai; Sun, Menghong; Zhao, Zhihua; Yang, Jianping; Chen, Kuisheng

doi:10.1007/s12032-015-0662-3

Cited by 9 publications

(9 citation statements)

References 15 publications

(14 reference statements)

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“…ESCC is the most prevalent histopathologic subtype of EC in central regions of China, especially in Henan province [ 14 ]. Despite of the recent rapid advances in the diagnosis and treatment, survival of ESCC patients with recurrence or metastasis remains unfavorable [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-cateninviaEzh2

Wang

Zhu

et al. 2016

Oncotarget

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Evidences have shown that lncRNAs involve in the initiation and progression of various cancers including esophageal squamous cell carcinoma (ESCC). The aberrant expression of lncRNA MALAT1 was investigated in 106 paired ESCC tissues and adjacent non-cancerous tissues by qRT-PCR. Down-regulated MALAT1 and Ezh2 over-expression plasmid were constructed respectively to analyze the expression of β-catenin, Lin28 and Ezh2 genes. We found that the MALAT1 expression level was higher in human ESCC tissues (P=0.0011), which was closely correlated with WHO grade (P=0.0395, P=0.0331), lymph node metastasis (P=0.0213) and prognosis (P=0.0294). Silencing of MALAT1 expression inhibited cell proliferation, migration and tumor sphere formation, while increasing cell apoptosis of esophageal cancer in vitro. Down-regulation of MALAT1 decreased the expression of β-catenin, Lin28 and Ezh2 genes, while over-expressed Ezh2 combined with MALAT1 down-regulation completely reversed the si-MALAT1-mediated repression of β-catenin and Lin28 in esophageal cancer cells. Animal experiments showed that knockdown of MALAT1 decreased tumor formation and improved survival. MALAT1 promotes the initiation and progression of ESCC, suggesting that inhibition of MALAT1 might be a potential target for treatment of ESCC.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-cateninviaEzh2

Wang

Zhu

et al. 2016

Oncotarget

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“…TIMP2 was shown to reduce the tube formation ability of the murine melanoma cell line B16 24 . Moreover, in esophageal carcinoma TIMP-2 expression is negatively correlated with lymph node metastasis via inhibition of MMPs 32 .…”

Section: Discussionmentioning

confidence: 99%

Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model

et al. 2019

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The deubiquitinase cylindromatosis (CYLD) is a well-known tumor suppressor, found to be down regulated in many cancer types including breast cancer, colon carcinoma and malignant melanoma. CYLD is suppressed in human melanoma cells by the transcriptional repressor SNAIL1 leading to an increase of their proliferative, invasive and migratory potential. To gain additional insights into the distinct function of this tumor suppressor gene a new mouse model Tg(Grm1)Cyld−/− was generated. Herewith, we demonstrate that Cyld-deficiency leads to earlier melanoma onset and accelerated tumor growth and metastasis in the GRM1 melanoma mouse model. First, RNA sequencing data revealed a potential role of CYLD in the regulation of genes involved in proliferation, migration and angiogenesis. Experiments using cell lines generated from both primary and metastatic melanoma tissue of Tg(Grm1) Cyld−/− and Tg(Grm1) Cyld+/+ mice confirmed that loss of CYLD enhances the proliferative and migratory potential, as well as the clonogenicity in vitro. Moreover, we could show that Cyld-knockout leads to increased vasculogenic mimicry and enhanced (lymph-) angiogenesis shown by tube formation assays, immunohistochemistry and mRNA expression analyses. In summary, our findings reveal new functional aspects of CYLD in the process of (lymph-) angiogenesis and demonstrate its importance in the early process of melanoma progression.

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“…Several studies demonstrate that serine proteinase inhibitor (serpin) functioned as a lymphangiogenesis inhibitor to suppress the lymphatic metastasis of cancer and the LECs proliferation and migration [35,36,37]. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) is lower or negative in patients with lymph node metastasis [38]. Furthermore, matrix metalloproteinases inhibitors are well recognized to impair lymphangiogenesis [39].…”

Section: Discussionmentioning

confidence: 99%

Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells

et al. 2019

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Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase Cδ (PKCδ), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKCδ, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis.

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Influence of lymphatic endothelial cells on proliferation and invasiveness of esophageal carcinoma cells in vitro and lymphangiogenesis in vivo

Cited by 9 publications

References 15 publications

Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-cateninviaEzh2

Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-cateninviaEzh2

Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model

Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells

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