ArticleCancer research2013
Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Organic small-molecule NIR-II fluorophores for tumor phototheranostics.Light, science & applications · 2026Review
- Bioactive Products Targeting C-Met As Potential Antitumour Drugs.Anti-cancer agents in medicinal chemistry · 2025Review
- The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Oncolytic vaccinia virus injected intravenously sensitizes pancreatic neuroendocrine tumors and metastases to immune checkpoint blockade.Molecular therapy oncolytics · 2022Article
- AHRR contributes to inflammatory lymphangiogenesis by activating the EPAS1/VEGFD signaling axis in head and neck cancer.American journal of cancer research · 2022Article
- Angiogenesis in NENs, with a focus on gastroenteropancreatic NENs: from biology to current and future therapeutic implications.Frontiers in oncology · 2022Review
- Review
- Review
- Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.Cancer research · 2021Article
- RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo.Biomedicines · 2021Article
- Article
- Targeted Therapies in the Management of Well-Differentiated Digestive and Lung Neuroendocrine Neoplasms.Current treatment options in oncology · 2020Review
- MET-dependent solid tumours - molecular diagnosis and targeted therapy.Nature reviews. Clinical oncology · 2020Review
- Medical Management of Gastroenteropancreatic Neuroendocrine Tumors.Surgical oncology clinics of North America · 2020Review
- MALAT1 regulates miR-34a expression in melanoma cells.Cell death & disease · 2019Article
- Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors.Oncogenesis · 2019Article
- Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy.Nature reviews. Cancer · 2018Review
- Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma.Molecular cancer · 2018Review
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inhibition of VEGF signaling can promote lymph node metastasis in preclinical models, but the mechanism is not fully understood, and successful methods of prevention have not been found. Signaling of hepatocyte growth factor (HGF) and its receptor c-Met can promote the growth of lymphatics and metastasis of some tumors. We sought to explore the contributions of c-Met signaling to lymph node metastasis after inhibition of VEGF signaling. In particular, we examined whether c-Met is upregulated in lymphatics in or near pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice and whether lymph node metastasis can be reduced by concurrent inhibition of VEGF and c-Met signaling. Inhibition of VEGF signaling by anti-VEGF antibody or sunitinib in mice from the age of 14 to 17 weeks was accompanied by more intratumoral lymphatics, more tumor cells inside lymphatics, and more lymph node metastases. Under these conditions, lymphatic endothelial cells, like tumor cells, had strong immunoreactivity for c-Met and phospho-c-Met. c-Met blockade by the selective inhibitor, PF-04217903, significantly reduced metastasis to local lymph nodes. Together, these results indicate that inhibition of VEGF signaling in RIP-Tag2 mice upregulates c-Met expression in lymphatic endothelial cells, increases the number of intratumoral lymphatics and number of tumor cells within lymphatics, and promotes metastasis to local lymph nodes. Prevention of lymph node metastasis by PF-04217903 in this setting implicates c-Met signaling in tumor cell spread to lymph nodes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.