ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Nicotine Reduces Survival via Augmentation of Paracrine HGF-MET Signaling in the Pancreatic Cancer Microenvironment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study.Scientific reports · 2016Trial
- Cotinine Promotes Cancer Cell Proliferation and mEnvironment & health (Washington, D.C.) · 2026Article
- Acetylcholine enhances HIF-1α signaling in pancreatic cancer cells under hypoxia through the nAChR-α7/PDPK1/YAP pathway.International journal of biological sciences · 2026Article
- Cell signaling and epigenetic regulation of nicotine-induced carcinogenesis.Environmental pollution (Barking, Essex : 1987) · 2024Review
- A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer.Annals of translational medicine · 2023Review
- Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types.International journal of molecular sciences · 2023Article
- Classification of Pancreatic Ductal Adenocarcinoma Using MALDI Mass Spectrometry Imaging Combined with Neural Networks.Cancers · 2023Article
- Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening.Current oncology (Toronto, Ont.) · 2022Review
- Article
- Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.Oncology letters · 2022Article
- The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth.Cancer cell international · 2021Review
- Pancreatic cancer: A review of epidemiology, trend, and risk factors.World journal of gastroenterology · 2021Review
- A nicotine-induced positive feedback loop between HIF1A and YAP1 contributes to epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2020Article
- The Impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives.Journal of cellular and molecular medicine · 2020Review
- From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2020Review
- Nicotine Induces IL-8 Secretion from Pancreatic Cancer Stroma and Worsens Cancer-Induced Cachexia.Cancers · 2020Article
- Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches.Radiation oncology (London, England) · 2019Review
- Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer.Oncotarget · 2018Article
- Effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma mortality: A retrospective cohort study consisting of 1783 patients.Scientific reports · 2017Article
- Cigarette Smoking and Pancreatic Cancer Survival.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe relationship between smoking and pancreatic cancer biology, particularly in the context of the heterogeneous microenvironment, remains incompletely defined. We hypothesized that nicotine exposure would lead to the augmentation of paracrine growth factor signaling between tumor-associated stroma (TAS) and pancreatic cancer cells, ultimately resulting in accelerated tumor growth and metastasis. EXPERIMENTAL
designThe effect of tobacco use on overall survival was analyzed using a prospectively maintained database of surgically resected patients with pancreatic cancer. Nicotine exposure was evaluated in vitro using primary patient-derived TAS and pancreatic cancer cells independently and in coculture. Nicotine administration was then assessed in vivo using a patient-derived pancreatic cancer xenograft model.
resultsContinued smoking was associated with reduced overall survival after surgical resection. In culture, nicotine-stimulated hepatocyte growth factor (HGF) secretion in primary patient-derived TAS and nicotine stimulation was required for persistent pancreatic cancer cell c-Met activation in a coculture model. c-Met activation in this manner led to the induction of inhibitor of differentiation-1 (Id1) in pancreatic cancer cells, previously established as a mediator of growth, invasion and chemoresistance. HGF-induced Id1 expression was abrogated by both epigenetic and pharmacologic c-Met inhibition. In patient-derived pancreatic cancer xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression by qRT-PCR and phospho-Met levels by ELISA. Similarly, elevated levels of phospho-Met in surgically resected pancreatic cancer specimens correlated with reduced overall survival.
conclusionsTaken together, these data demonstrate a novel, microenvironment-dependent paracrine signaling mechanism by which nicotine exposure promotes the growth and metastasis of pancreatic cancer.
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