ArticleNeoplasia (New York, N.Y.)2009
Depletion of serotonin and selective inhibition of 2B receptor suppressed tumor angiogenesis by inhibiting endothelial nitric oxide synthase and extracellular signal-regulated kinase 1/2 phosphorylation.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
- Review
- Cancer and neurotransmitter receptors.Chinese medical journal · 2025Review
- Serotonergic Regulation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Context-dependent roles of 5-HT and its receptors in tumor growth and wound healing: Mechanisms and therapeutic implications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- Involvement of neuronal factors in tumor angiogenesis and the shaping of the cancer microenvironment.Frontiers in immunology · 2024Review
- HInternational journal of molecular sciences · 2022Article
- An Overview of the Molecular Cues and Their Intracellular Signaling Shared by Cancer and the Nervous System: From Neurotransmitters to Synaptic Proteins, Anatomy of an All-Inclusive Cooperation.International journal of molecular sciences · 2022Review
- Transcription Profile and Pathway Analysis of the Endocannabinoid Receptor Inverse Agonist AM630 in the Core and Infiltrative Boundary of Human Glioblastoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Association between antipsychotic agents and risk of lung cancer: a nested case-control study.Cancer communications (London, England) · 2022Article
- A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression.Frontiers in oncology · 2022Article
- The Nervous System Contributes to the Tumorigenesis and Progression of Human Digestive Tract Cancer.Journal of immunology research · 2022Review
- A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression.Metabolites · 2021Article
- Network pharmacology-based and clinically relevant prediction of active ingredients and potential targets of Chinese herbs on stage IV lung adenocarcinoma patients.Journal of cancer research and clinical oncology · 2021Article
- Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer.Nutrients · 2021Review
- Serotonin Pathway in Cancer.International journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis.Scientific reports · 2020Article
- Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers.Pathology oncology research : POR · 2020Article
- Neurotransmitters: emerging targets in cancer.Oncogene · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effects of serotonin (5-HT) on tumor growth are inconsistent. We investigated whether a decreased level of 5-HT affected tumor growth using 5-HT transporter knockout (5-HTT(-/-)) mice, which showed 5-HT depletion. When cancer cells were injected subcutaneously into both 5-HTT(-/-) and 5-HTT(+/+) mice, the tumor growth was markedly attenuated in 5-HTT(-/-) mice. Serotonin levels in the blood, forebrain, and tumors of 5-HTT(-/-) mice bearing tumors were significantly smaller than those of their 5-HTT(+/+) littermates. However, 5-HT did not increase cancer cells' proliferation in vitro. When we applied 5-HTT inhibitors to the wild mice bearing tumors, they did not inhibit tumor growth. The endothelial nitric oxide synthase (eNOS) expressions in tumors were reduced in 5-HTT(-/-) mice compared with 5-HTT(+/+) mice. Stimulations with 5-HT (1-50 microM) induced eNOS expressions in human umbilical vein endothelial cell (HUVEC) in a concentration-dependent manner. When we measured activations of multiple signaling pathways by using a high-throughput phosphospecific antibodies platform, 5-HT stimulated the extracellular signal-regulated kinase 1/2 (ERK1/2) in HUVEC. Moreover, we found that the physiological level of 5-HT induced phosphorylation of both ERK1/2 and eNOS in HUVEC. Human umbilical vein endothelial cell expressed both 5-HT(2B) and 5-HT(2C) receptors. SB204741, a specific 5-HT(2B) receptor inhibitor, blocked 5-HT-induced ERK1/2 and eNOS phosphorylations, whereas RS102221, a specific 5-HT(2C) receptor inhibitor, did not in HUVEC. SB204741 reduced microvessel density in tumors and inhibited the proliferation of HUVEC in vitro. These results suggest that regulation of 5-HT and 5-HT receptors, especially the 5-HT(2B) receptor, may serve as a therapeutic strategy in cancer therapy.
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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.