ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Effect of Metformin Use on Survival in Resectable Pancreatic Cancer: A Single-Institution Experience and Review of the Literature.PloS one · 2016Pooled it
- Association between PLVAP downregulation and increased lymphocyte infiltration in newly diagnosed glioblastoma treated with bevacizumab.Brain tumor pathology · 2026Article
- Metabolic Endotoxemia Amplifies Estrogen Signaling Through Stromal Crosstalk in Obesity-Associated Breast Cancer.International journal of molecular sciences · 2026Article
- The Prognostic and Biological Value of PGF-Based H&E Pathomics in Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Impact of ligand binding on VEGFR1, VEGFR2, and NRP1 localization in human endothelial cells.PLoS computational biology · 2025Article
- The Role of Perirenal Adipose Tissue in Carcinogenesis-From Molecular Mechanism to Therapeutic Perspectives.Cancers · 2025Review
- Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- Extracellular vesicles-miR-205-5p inhibits lymphatic metastasis in pancreatic cancer through diffusely downregulating VEGFA.Journal of Cancer · 2025Article
- Prognostic Value of PlGF Upregulation in Prostate Cancer.Biomedicines · 2024Article
- FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.EMBO molecular medicine · 2024Article
- Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2024Review
- Body Weight Correlates with Molecular Variances in Patients with Cancer.Cancer research · 2024Article
- Receptor tyrosine kinases in breast cancer treatment: unraveling the potential.American journal of cancer research · 2024Review
- Spatial and Temporal Trends in Pancreatic Cancer Burden Attributable to High Body Mass Index at the Global and National Levels.Journal of epidemiology and global health · 2023Article
- Hemosiderin-Laden Macrophages in Canine Mammary Carcinomas.Animals : an open access journal from MDPI · 2023Article
- Decoding the obesity-cancer connection: lessons from preclinical models of pancreatic adenocarcinoma.Life science alliance · 2023Review
- Metamorphic Effect of Angiogenic Switch in Tumor Development: Conundrum of Tumor Angiogenesis Toward Progression and Metastatic Potential.Biomedicines · 2023Review
- Article
- The multifaceted role of placental growth factor in the pathogenesis and progression of bronchial asthma and pulmonary fibrosis: Therapeutic implications.Genes & diseases · 2023Review
- Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.Journal of pharmaceutical analysis · 2023Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 11 institutions in 7 countries.
Funding
Abstract
purposeObesity promotes pancreatic and breast cancer progression via mechanisms that are poorly understood. Although obesity is associated with increased systemic levels of placental growth factor (PlGF), the role of PlGF in obesity-induced tumor progression is not known. PlGF and its receptor VEGFR-1 have been shown to modulate tumor angiogenesis and promote tumor-associated macrophage (TAM) recruitment and activity. Here, we hypothesized that increased activity of PlGF/VEGFR-1 signaling mediates obesity-induced tumor progression by augmenting tumor angiogenesis and TAM recruitment/activity. EXPERIMENTAL
designWe established diet-induced obese mouse models of wild-type C57BL/6, VEGFR-1 tyrosine kinase (TK)-null, or PlGF-null mice, and evaluated the role of PlGF/VEGFR-1 signaling in pancreatic and breast cancer mouse models and in human samples.
resultsWe found that obesity increased TAM infiltration, tumor growth, and metastasis in pancreatic cancers, without affecting vessel density. Ablation of VEGFR-1 signaling prevented obesity-induced tumor progression and shifted the tumor immune environment toward an antitumor phenotype. Similar findings were observed in a breast cancer model. Obesity was associated with increased systemic PlGF, but not VEGF-A or VEGF-B, in pancreatic and breast cancer patients and in various mouse models of these cancers. Ablation of PlGF phenocopied the effects of VEGFR-1-TK deletion on tumors in obese mice. PlGF/VEGFR-1-TK deletion prevented weight gain in mice fed a high-fat diet, but exacerbated hyperinsulinemia. Addition of metformin not only normalized insulin levels but also enhanced antitumor immunity.
conclusionsTargeting PlGF/VEGFR-1 signaling reprograms the tumor immune microenvironment and inhibits obesity-induced acceleration of tumor progression. Clin Cancer Res; 22(12); 2993-3004. ©2016 AACR.
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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.