ArticleOncotarget2016
Pancreatic stellate cells contribute pancreatic cancer pain via activation of sHH signaling pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- The nociceptor primary cilium.Brain : a journal of neurology · 2026Review
- Understanding the Pathophysiology of Chronic Pancreatitis: A Comprehensive Review Unraveling Pain Mechanisms and the Role of Psychosocial Factors.Journal of clinical medicine · 2026Review
- Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.International journal of medical sciences · 2026Review
- Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.British journal of cancer · 2025Article
- TGF-β1/SMAD3-mediated Non-canonical Hedgehog Signaling Promotes Pancreatic Stellate Cell Activation and Fibrosis in Chronic Pancreatitis.International journal of biological sciences · 2025Article
- Nanomedicine regulating PSC-mediated intercellular crosstalk: Mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2024Review
- Unraveling the interplay: exploring signaling pathways in pancreatic cancer in the context of pancreatic embryogenesis.Frontiers in cell and developmental biology · 2024Review
- Role of sonic hedgehog signaling pathway in the regulation of ion channels: focus on its association with cardio-cerebrovascular diseases.Journal of physiology and biochemistry · 2023Review
- Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.Neurochemical research · 2023Review
- Secondary iron overload induces chronic pancreatitis and ferroptosis of acinar cells in mice.International journal of molecular medicine · 2023Article
- Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance.Cancers · 2022Review
- Review
- Recent advances in understanding pancreatic cancer.Faculty reviews · 2022Review
- CGRP: A New Endogenous Cell Stemness Maintenance Molecule.Oxidative medicine and cellular longevity · 2022Review
- Pancreatic stellate cells - rising stars in pancreatic pathologies.Physiological research · 2021Review
- Shedding Light on the Role of Neurotransmitters in the Microenvironment of Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
- Targeting HGF/c-MET Axis in Pancreatic Cancer.International journal of molecular sciences · 2020Review
- NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway.Journal of cellular and molecular medicine · 2020Article
- Animal Models of Cancer-Related Pain: Current Perspectives in Translation.Frontiers in pharmacology · 2020Review
- Prognostic Signatures Based on Thirteen Immune-Related Genes in Colorectal Cancer.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abdominal pain is a critical clinical symptom in pancreatic cancer (PC) that affects the quality of life for PC patients. However, the pathogenesis of PC pain is largely unknown. In this study, we show that PC pain is initiated by the sonic hedgehog (sHH) signaling pathway in pancreatic stellate cells (PSCs), which is activated by sHH secreted from PC cells, and then, neurotrophic factors derived from PSCs mediate the pain. The different culture systems were established in vitro, and the expression of sHH pathway molecules, neurotrophic factors, TRPV1, and pain factors were examined. Capsaicin-evoked TRPV1 currents in dorsal root ganglion (DRG) neurons were examined by the patch-clamp technique. Pain-related behavior was observed in an orthotopic tumor model. sHH and PSCs increased the expression and secretion of TRPV1, SP, and CGRP by inducing NGF and BDNF in a co-culture system, also increasing TRPV1 current. But, suppressing sHH pathway or NGF reduced the expression of TRPV1, SP, and CGRP. In vivo, PSCs and PC cells that expressed high levels of sHH could enhance pain behavior. Furthermore, the blockade of NGF or TRPV1 significantly attenuated the pain response to mechanical stimulation compared with the control. Our results demonstrate that sHH signaling pathway is involved in PC pain, and PSCs play an essential role in the process greatly by inducing NGF.
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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.