ArticleGut2012
Inhibition of histidine decarboxylase ablates the autocrine tumorigenic effects of histamine in human cholangiocarcinoma.
Article in Gut, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 78 citations in OpenAlex.
- Histamine is a molecular transducer of adaptation to endurance exercise training in humans.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Trial
- Evidence of a broad histamine footprint on the human exercise transcriptome.The Journal of physiology · 2016Trial
- Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease.Genes & diseases · 2027Article
- Overexpression of histidine decarboxylase promotes cancer cell apoptosis and migration in HN5 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- High histamine expression by early-stage squamous cell carcinoma of the tongue is associated with a poor prognosis.Histology and histopathology · 2026Article
- Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.Life (Basel, Switzerland) · 2024Review
- HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.Frontiers in pharmacology · 2024Article
- Article
- Few, but Efficient: The Role of Mast Cells in Breast Cancer and Other Solid Tumors.Cancer research · 2022Review
- Review
- HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2022Article
- Mast cells in liver disease progression: An update on current studies and implications.Hepatology (Baltimore, Md.) · 2022Review
- Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.EMBO molecular medicine · 2021Article
- Recent Advances in the Mechanism Research and Clinical Treatment of Anti-Angiogenesis in Biliary Tract Cancer.Frontiers in oncology · 2021Review
- Biliary damage and liver fibrosis are ameliorated in a novel mouse model lacking l-histidine decarboxylase/histamine signaling.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Modulation of the Tryptophan Hydroxylase 1/Monoamine Oxidase-A/5-Hydroxytryptamine/5-Hydroxytryptamine Receptor 2A/2B/2C Axis Regulates Biliary Proliferation and Liver Fibrosis During Cholestasis.Hepatology (Baltimore, Md.) · 2020Article
- Review
- Histamine receptors and cancer pharmacology: an update.British journal of pharmacology · 2020Review
- Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma.Oncogene · 2020Article
- Inflammation and Progression of Cholangiocarcinoma: Role of Angiogenic and Lymphangiogenic Mechanisms.Frontiers in medicine · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundIn several tumours the endogenous activity of histidine decarboxylase (HDC), the enzyme stimulating histamine synthesis, sustains the autocrine trophic effect of histamine on cancer progression. Cholangiocarcinoma is a biliary cancer with limited treatment options. Histamine interacts with four G-protein coupled receptors, H1-H4 histamine receptors (HRs).
objectiveTo determine the effects of histamine stimulation and inhibition of histamine synthesis (by modulation of HDC) on cholangiocarcinoma growth.
methodsIn vitro studies were performed using multiple human cholangiocarcinoma lines. The expression levels of the histamine synthetic machinery and HRs were evaluated along with the effects of histamine stimulation and inhibition on cholangiocarcinoma proliferation. A xenograft tumour model was used to measure tumour volume after treatment with histamine or inhibition of histamine synthesis by manipulation of HDC. Vascular endothelial growth factor (VEGF) expression was measured in cholangiocarcinoma cells concomitant with the evaluation of the expression of CD31 in endothelial cells in the tumour microenvironment.
resultsCholangiocarcinoma cells display (1) enhanced HDC and decreased monoamine oxidase B expression resulting in increased histamine secretion; and (2) increased expression of H1-H4 HRs. Inhibition of HDC and antagonising H1HR decreased histamine secretion in Mz-ChA-1 cells. Long-term treatment with histamine increased proliferation and VEGF expression in cholangiocarcinoma that was blocked by HDC inhibitor and the H1HR antagonist. In nude mice, histamine increased tumour growth (up to 25%) and VEGF expression whereas inhibition of histamine synthesis (by reduction of HDC) ablated the autocrine stimulation of histamine on tumour growth (~80%) and VEGF expression. No changes in angiogenesis (evaluated by changes in CD31 immunoreactivity) were detected in the in vivo treatment groups.
conclusionThe novel concept that an autocrine loop (consisting of enhanced histamine synthesis by HDC) sustains cholangiocarcinoma growth is proposed. Drug targeting of HDC may be important for treatment of patients with cholangiocarcinoma.
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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.