ArticleCancer biology & therapy2011
Knockdown of VEGF receptor-1 (VEGFR-1) impairs macrophage infiltration, angiogenesis and growth of clear cell renal cell carcinoma (CRCC).
Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 70 citations in OpenAlex.
- VEGF-A blockade overcomes liver metastases resistance to chemoimmunotherapy in patients with advanced non-squamous NSCLC.Journal for immunotherapy of cancer · 2026Article
- Interplay of HIF-1α, SMAD2, and VEGF signaling in hypoxic renal environments: impact on macrophage polarization and renoprotection.Renal failure · 2025Article
- The dual role of VEGF-A in a complex in vitro model of oxaliplatin-induced neurotoxicity: Pain-related and neuroprotective effects.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Emerging macrophage-based therapies for cancer: a review of preclinical and clinical advances.Frontiers in immunology · 2025Review
- CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.Journal of translational medicine · 2023Article
- Blocking CD47 Shows Superior Anti-tumor Therapeutic Effects of Bevacizumab in Gastric Cancer.Frontiers in pharmacology · 2022Article
- Roles of the Dynamic Tumor Immune Microenvironment in the Individualized Treatment of Advanced Clear Cell Renal Cell Carcinoma.Frontiers in immunology · 2021Review
- Fruquintinib inhibits VEGF/VEGFR2 axis of choroidal endothelial cells and M1-type macrophages to protect against mouse laser-induced choroidal neovascularization.Cell death & disease · 2020Article
- Changes of expression levels of serum cystatin C and soluble vascular endothelial growth factor receptor 1 in the treatment of patients with glomerulus nephritis.Experimental and therapeutic medicine · 2020Article
- RCC Immune Microenvironment Subsequent to Targeted Therapy: A Friend or a Foe?Frontiers in oncology · 2020Review
- PARP inhibition and immune modulation: scientific rationale and perspectives for the treatment of gynecologic cancers.Therapeutic advances in medical oncology · 2020Review
- Targeting the Tumor Microenvironment in Renal Cell Cancer Biology and Therapy.Frontiers in oncology · 2019Review
- Risk of bleeding associated with antiangiogenic monoclonal antibodies bevacizumab and ramucirumab: a meta-analysis of 85 randomized controlled trials.OncoTargets and therapy · 2018Article
- Article
- CMTM5 inhibits renal cancer cell growth through inducing cell-cycle arrest and apoptosis.Oncology letters · 2017Article
- Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding.Oncotarget · 2016Article
- Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells.Oncology letters · 2016Article
- Carcinogenesis of renal cell carcinoma reflected in HLA ligands: A novel approach for synergistic peptide vaccination design.Oncoimmunology · 2016Article
- Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward?Cancer biology & medicine · 2016Article
- Tumor Associated Macrophages in Kidney Cancer.Analytical cellular pathology (Amsterdam) · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Angiogenesis is essential for tumor growth and metastasis. VEGF has been shown to be a central player in this process. The biological activity of VEGF is mainly mediated by two tyrosine kinase receptors, VEGFR-1 and VEGFR-2. While increasing evidence suggests that VEGF/VEGFR-1 signaling is crucial for tumor angiogenesis, its molecular mechanism is not well understood. Here we show that VEGFR-1 knockdown dramatically inhibits tumor growth. This inhibition is associated with significant decrease of tumor VEGF levels and tumor angiogenesis as well as an increased tumor necrosis. Moreover, we demonstrate that VEGF in CRCC tumors is mainly produced by tumor stromal cells instead of the tumor cells themselves. It has been shown that macrophages constitute a significant part of tumor stromal cells and produce a large amount of VEGF. We therefore examined the macrophage infiltration in the xenograft tumors. Remarkably, VEGFR-1 knockdown attenuates the tumor macrophages infiltration. To understand the mechanism, we investigated the impact of VEGFR-1 knockdown on the expression of monocyte chemoattractant protein-1 (MCP-1), one of the main chemoattractants for macrophages. Significantly, VEGFR-1 knockdown inhibits MCP-1 expression of CRCC cells. Taken together, these data indicate that VEGF/VEGFR-1 signaling plays an essential role in initiating tumor angiogenesis by regulating MCP-1 expression, which in turn, attracts macrophages infiltration and VEGF production. Thus, these studies suggest that blockade of VEGFR-1 function may provide a tumor-specific, VEGF-based therapeutic strategy for treatment of CRCC.
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