ArticleBMC cancer2013
Anti-lymphangiogenic properties of mTOR inhibitors in head and neck squamous cell carcinoma experimental models.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- The combined signatures of programmed cell death and immune landscape provide a prognostic and therapeutic biomarker in the hepatocellular carcinoma.Frontiers in chemistry · 2024Article
- Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis inOncotarget · 2023Article
- Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis.Scientific reports · 2021Article
- Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2021Article
- CSgator: an integrated web platform for compound set analysis.Journal of cheminformatics · 2019Article
- Rapamycin suppresses angiogenesis and lymphangiogenesis in melanoma by downregulating VEGF-A/VEGFR-2 and VEGF-C/VEGFR-3 expression.OncoTargets and therapy · 2019Article
- [Changes of lymphatic vessel density in lung adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma and the regulatory factors].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- Gene expression profiling to predict recurrence of advanced squamous cell carcinoma of the tongue: discovery and external validation.Oncotarget · 2017Article
- Article
- Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2(-) Tumor Related to Lymphangioleiomyomatosis.The American journal of pathology · 2016Article
- The Fate of the Tumor in the Hands of Microenvironment: Role of TAMs and mTOR Pathway.Mediators of inflammation · 2016Review
- Rapamycin targets Interleukin 6 (IL-6) expression and suppresses endothelial cell invasion stimulated by tumor cells.American journal of translational research · 2016Article
- Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity.PloS one · 2015Article
- mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations.Journal of the National Cancer Institute · 2014Article
- mTOR Inhibition: From Aging to Autism and Beyond.Scientifica · 2013Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundTumor dissemination to cervical lymph nodes via lymphatics represents the first step in the metastasis of head and neck squamous cell carcinoma (HNSCC) and is the most significant predictor of tumor recurrence decreasing survival by 50%. The lymphatic suppressing properties of mTOR inhibitors are not yet well understood.
methodsLymphatic inhibiting effects of rapamycin were evaluated in vitro using two lymphatic endothelial cell (LEC) lines. An orthotopic mouse model of HNSCC (OSC-19 cells) was used to evaluate anti-lymphangiogenic effects of rapamycin in vivo. The incidence of cervical lymph node metastases, numbers of tumor-free lymphatic vessels and those invaded by tumor cells in mouse lingual tissue, and expression of pro-lymphangiogenic markers were assessed.
resultsRapamycin significantly decreased lymphatic vascular density (p = 0.027), reduced the fraction of lymphatic vessels invaded by tumor cells in tongue tissue (p = 0.013) and decreased metastasis-positive lymph nodes (p = 0.04). Rapamycin also significantly attenuated the extent of metastatic tumor cell spread within lymph nodes (p < 0.0001). We found that rapamycin significantly reduced LEC proliferation and was correlated with decreased VEGFR-3 expression in both LEC, and in some HNSCC cell lines.
conclusionsThe results of this study demonstrate anti-lymphangiogenic properties of mTOR inhibitors in HNSCC. mTOR inhibitors suppress autocrine and paracrine growth stimulation of tumor and lymphatic endothelial cells by impairing VEGF-C/VEGFR-3 axis and release of soluble VEGFR-2. In a murine HNSCC orthotopic model rapamycin significantly suppressed lymphovascular invasion, decreased cervical lymph node metastasis and delayed the spread of metastatic tumor cells within the lymph nodes.
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