ArticleCell communication and signaling : CCS2019
Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 59 citations in OpenAlex.
- Hypoxia-Driven CA2 Promotes Trophoblast Dysfunction in Preeclampsia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Carbonic Anhydrase I and II as Biomarkers and Therapeutic Targets in Human Disease: From Physiology to Clinical Translation.International journal of molecular sciences · 2026Review
- Discovery of indolylchalcone benzenesulfonamides as selective inhibitors of tumor-associated carbonic anhydrase IX and XII.Scientific reports · 2026Article
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Integrated computational analysis prioritizes candidate targets and pathways linking ochratoxin A exposure to hepatocellular carcinoma.PloS one · 2026Article
- Identification of ion homeostasis-related genes as diagnostic biomarkers for pulmonary arterial hypertension via WGCNA and machine learning.Frontiers in genetics · 2026Article
- The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.Journal of bone oncology · 2025Review
- Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma.Annals of surgical oncology · 2025Article
- SLC4A7 suppresses lung adenocarcinoma oncogenesis by reducing lactate transport and protein lactylation.International journal of oncology · 2025Article
- Single-cell sequencing reveals dysregulated cell type perturbations and critical mediator communication remodelling in colorectal cancer.Frontiers in immunology · 2025Article
- Beyond pain relief: the thrombosis threat of celecoxib.Therapeutic advances in drug safety · 2025Article
- Regulatory role and therapeutic prospect of lactate modification in cancer.Frontiers in pharmacology · 2025Review
- Beyond starving cancer: anti-angiogenic therapy.Journal of medical ultrasonics (2001) · 2024Review
- An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.British journal of cancer · 2024Article
- Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.Molecular biology reports · 2024Review
- CRISPR-Cas9-mediated deletion of carbonic anhydrase 2 in the ciliary body to treat glaucoma.Cell reports. Medicine · 2024Article
- Cancer-triggered systemic disease and therapeutic targets.Holistic integrative oncology · 2024Article
- Carbonic anhydrase, its inhibitors and vascular function.Frontiers in molecular biosciences · 2024Review
- Single-cell transcriptomic analysis of gingivo-buccal oral cancer reveals two dominant cellular programs.Cancer science · 2023Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood. METHODOLOGY: The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia.
resultsThe present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis.
conclusionThese findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy. Video Abstract.
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