ArticleMed (New York, N.Y.)2021
LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency.
Article in Med (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Intracellular LRG1 recruits MARCH2 to ubiquitinate and degrade endothelial VE-cadherin in septic lung injury.Acta pharmacologica Sinica · 2026Article
- Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.Human cell · 2026Review
- Review
- LRG1 as a Potential Therapeutic Target in Atherosclerosis: Mechanistic Basis and Current Evidence.Cells · 2026Review
- Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.Cellular & molecular immunology · 2026Article
- Early Transcriptional Changes in Neutrophil-Mediated Processes Following Recanalization After Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Endothelial cell-derived IGFBP7 suppresses angiogenesis and tumor progression in colorectal cancer via the VAPA-TGF-β1 pathway.Journal of experimental & clinical cancer research : CR · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.Nature reviews. Immunology · 2026Review
- Review
- Brucein D suppresses breast cancer proliferation and migration via targeting the FAK/LRG1 signaling pathway.Scientific reports · 2025Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Leucine-rich α-2-glycoprotein 1 initiates the onset of diabetic retinopathy in mice.Science translational medicine · 2025Article
- Tumor suppressors in Sox2-mediated lung cancers promote distinct cell-intrinsic and immunologic remodeling.JCI insight · 2025Article
- Article
- Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice.Clinical and translational medicine · 2025Review
- Leucine-rich α-2 glycoprotein 1 (LRG1) during inflammatory complications after allogeneic stem cell transplantation and CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Article
- Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling.Gastroenterology · 2025Article
- LRG1 inhibition promotes acute pancreatitis recovery by inducing cholecystokinin Type 1 receptor expression via Akt.Theranostics · 2025Article
- Apolipoproteins have a major role in cellular tumor dormancy in triple negative breast cancer: In-silico study.Scientific reports · 2024Article
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Authors and funding
20 authors at 6 institutions in 6 countries.
Funding
Abstract
backgroundA poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization. Here, we investigate whether LRG1 in tumors is vasculopathic and whether its inhibition has therapeutic utility.
methodsTumor growth and vascular structure were analyzed in subcutaneous and genetically engineered mouse models in wild-type and Lrg1 knockout mice. The effects of LRG1 antibody blockade as monotherapy, or in combination with co-therapies, on vascular function, tumor growth, and infiltrated lymphocytes were investigated.
findingsIn mouse models of cancer, Lrg1 expression was induced in tumor endothelial cells, consistent with an increase in protein expression in human cancers. The expression of LRG1 affected tumor progression as Lrg1 gene deletion, or treatment with a LRG1 function-blocking antibody, inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function, resulting in enhanced efficacy of cisplatin chemotherapy, adoptive T cell therapy, and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent to immune active.
conclusionsLRG1 drives vascular abnormalization, and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics.
fundingWellcome Trust (206413/B/17/Z), UKRI/MRC (G1000466, MR/N006410/1, MC/PC/14118, and MR/L008742/1), BHF (PG/16/50/32182), Health and Care Research Wales (CA05), CRUK (C42412/A24416 and A17196), ERC (ColonCan 311301 and AngioMature 787181), and DFG (CRC1366).
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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.