ArticleOncoTargets and therapy2019
Sympathetic innervation contributes to perineural invasion of salivary adenoid cystic carcinoma via the β2-adrenergic receptor.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Schwann Cells in Physical Nerve Injury and Tumor Perineural Invasion: A Functional Overview and Comparison.Cancer medicine · 2026Review
- Current landscape and future directions of therapeutic approaches for adenoid cystic carcinoma of the salivary glands (Review).Oncology letters · 2025Review
- Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.Diagnostics (Basel, Switzerland) · 2024Review
- Understanding the role of nerves in head and neck cancers - a review.Oncology reviews · 2024Review
- The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.Hepatology international · 2023Article
- Review
- Nerves in the Tumor Microenvironment: Origin and Effects.Frontiers in cell and developmental biology · 2020Review
- Biobehavioral Pathways and Cancer Progression: Insights for Improving Well-Being and Cancer Outcomes.Integrative cancer therapiesReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePerineural invasion (PNI) is reported to correlate with local recurrence and poor prognosis of salivary adenoid cystic carcinoma (SACC). However, the pathogenesis of PNI remains unclear. The aims of this study were to investigate the correlation between sympathetic innervation and SACC PNI and to elucidate how the sympathetic neurotransmitter norepinephrine (NE) regulates the PNI process. MATERIALS AND
methodsSympathetic innervation and β2-adrenergic receptor (β2-AR) expression in SACC tissues were evaluated by immunohistochemistry. The NE concentrations in SACC tissues and dorsal root ganglia (DRG) coculture models were measured by ELISA. β2-AR expression in SACC cells was detected by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence assay. SACC cells were treated with NE, the nonselective α-AR blocker phentolamine, the β2-AR antagonist ICI118,551, or were transfected with β2-AR small interfering RNA (siRNA). Proliferation was evaluated in methyl thiazolyl tetrazolium assay, and migration was evaluated in Transwell assay and wound-healing assay. PNI was tested through both Transwell assay and a DRG coculture model. The expressions of epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs) were measured by performing qRT-PCR and Western blot assay.
resultsSympathetic innervation and β2-AR were highly distributed in SACC tissues and correlated positively with PNI (
conclusionCollectively, our findings reveal the supportive role of sympathetic innervation in the pathogenesis of SACC PNI and suggest β2-AR as a potential therapeutic target for treating PNI in SACC.
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