ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Synergistic effects of mTOR inhibitors with VEGFR3 inhibitors on the interaction between TSC2-mutated cells and lymphatic endothelial cells.Science China. Life sciences · 2025Article
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Targeting fibroblast-endothelial cell interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics.JCI insight · 2025Article
- Targeting Fibroblast-Endothelial Interactions in LAM Pathogenesis: 3D Spheroid and Spatial Transcriptomic Insights for Therapeutic Innovation.bioRxiv : the preprint server for biology · 2024Article
- Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1.The Journal of clinical investigation · 2023Article
- An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss.Nature communications · 2022Article
- Case report: Kidney perivascular epithelioid cell tumor treated with anti-VEGFR tyrosine kinase inhibitor and MTOR inhibitor.Frontiers in oncology · 2022Article
- High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma.Human genomics · 2021Article
- mTORC1 stimulates cell growth through SAM synthesis and mMolecular cell · 2021Article
- Role of lymphatic endothelial cells in the tumor microenvironment-a narrative review of recent advances.Translational lung cancer research · 2021Review
- Editorial: Advances and Updates in Diffuse Cystic Lung Diseases.Frontiers in medicine · 2021Article
- Zoledronic acid inhibits TSC2-null cell tumor growth via RhoA/YAP signaling pathway in mouse models of lymphangioleiomyomatosis.Cancer cell international · 2020Article
- Case Report: Gastrointestinal PEComa WithFrontiers in oncology · 2020Article
- Possible Novel Therapeutic Targets in Lymphangioleiomyomatosis Treatment.Frontiers in medicine · 2020Review
- Article
- Review
- TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti-PD-1/anti-CTLA-4 immunotherapy.JCI insight · 2018Article
- Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation.Cancer research · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary lymphangioleiomyomatosis (LAM), a rare progressive lung disease associated with mutations of the tuberous sclerosis complex 2 (Tsc2) tumor suppressor gene, manifests by neoplastic growth of LAM cells, induction of cystic lung destruction, and respiratory failure. LAM severity correlates with upregulation in serum of the prolymphangiogenic vascular endothelial growth factor D (VEGF-D) that distinguishes LAM from other cystic diseases. The goals of our study was to determine whether Tsc2 deficiency upregulates VEGF-D, and whether axitinib, the Food and Drug Administration-approved small-molecule inhibitor of VEGF receptor (VEGFR) signaling, will reduce Tsc2-null lung lesion growth in a mouse model of LAM. Our data demonstrate upregulation of VEGF-D in the serum and lung lining in mice with Tsc2-null lesions. Progressive growth of Tsc2-null lesions induces recruitment and activation of inflammatory cells and increased nitric oxide production. Recruited cells isolated from the lung lining of mice with Tsc2-null lesions demonstrate upregulated expression of provasculogenic Vegfa, prolymphangiogenic Figf, and proinflammatory Nos2, Il6, and Ccl2 genes. Importantly, axitinib is an effective inhibitor of Tsc2-null lesion growth and inflammatory cell recruitment, which correlates with reduced VEGF-D levels in serum and lung lining. Our data demonstrate that pharmacological inhibition of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth, attenuates recruitment and activation of inflammatory cells, and reduces VEGF-D levels systemically and in the lung lining. Our study suggests a potential therapeutic benefit of inhibition of VEGFR signaling for treatment of LAM.
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Registered trials
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