ArticleBrain, behavior, and immunity2009
Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression.
Article in Brain, behavior, and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 2 of them syntheses that pooled it.
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Who cites it
169 citing papers in PubMed, 2 syntheses or guidelines pooled it, 320 citations in OpenAlex.
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- Integrative bioinformatic and experimental analysis reveals prognostic and immunological roles of psychological stress-related genes in skin cutaneous melanoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
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- Exploring β3-Adrenergic Receptor, HIF-1α, and CD31 Interplay in the Microenvironment of Atypical Melanocytic Lesions.Dermatopathology (Basel, Switzerland) · 2026Article
- Chronic stress and cancer progression through neuro‑endocrine‑immune networks (Review).Oncology reports · 2026Review
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- Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.Journal of neuroinflammation · 2026Review
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- The effects of housing temperature on mouse physiology and implications for disease modeling.Lab animal · 2026Review
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- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
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- Neural regulation of lung cancer: from mechanisms to clinical implications.European journal of medical research · 2025Review
- Pharmacological interventions targeting β-adrenoceptors in colorectal cancer: an evolving paradigm.Inflammopharmacology · 2025Review
109 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Studies suggest that stress can be a co-factor for the initiation and progression of cancer. The catecholamine stress hormone, norepinephrine (NE), may influence tumor progression by modulating the expression of factors implicated in angiogenesis and metastasis. The goal of this study was to examine the influence of NE on the expression of VEGF, IL-8, and IL-6 by the human melanoma cell lines, C8161, 1174MEL, and Me18105. Cells were treated with NE and levels of VEGF, IL-8, and IL-6 were measured using ELISA and real-time PCR. The expression of beta-adrenergic receptors (beta-ARs) mRNA and protein were also assessed. Finally, immunohistochemistry was utilized to examine the presence of beta1- and beta2-AR in primary and metastatic human melanoma biopsies. We show that NE treatment upregulated production of VEGF, IL-8, and IL-6 in C8161 cells and to a lesser extent 1174MEL and Me18105 cells. The upregulation was associated with induced gene expression. The effect on C8161 cells was mediated by both beta1- and beta2-ARs. Furthermore, 18 of 20 melanoma biopsies examined expressed beta2-AR while 14 of 20 melanoma biopsies expressed beta1-AR. Our data support the hypothesis that NE can stimulate the aggressive potential of melanoma tumor cells, in part, by inducing the production VEGF, IL-8, and IL-6. This line of research further suggests that interventions targeting components of the activated sympathetic-adrenal medullary (SAM) axis, or the utilization of beta-AR blocking agents, may represent new strategies for slowing down the progression of malignant disease and improving cancer patients' quality of life.
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