ArticleThe Journal of clinical investigation2011
Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer.iScience · 2026Article
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- NR4A2 induces perineural invasion in head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma via CXCL5/CXCR2 signaling axis.Cancer letters · 2026Article
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- Unlocking the Power of CXCR2 Inhibition to Overcome Gemcitabine Resistance in Pancreatic Cancer.FASEB bioAdvances · 2026Article
- Blockade of CC chemokine receptor 2 suppresses pancreatic cancer progression through the interaction with macrophages in the tumor microenvironment.Scientific reports · 2025Article
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- From infection to tumor: genetic evidence of viral antibody immune response' role in urologic cancer development.Discover oncology · 2025Article
- CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting.Cancer metastasis reviews · 2025Review
- The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy.European journal of immunology · 2024Review
- A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy.Scientific reports · 2024Article
- Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies.Frontiers in medicine · 2024Review
- Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target.Frontiers in immunology · 2024Review
- Inhibiting stromal Class I HDACs curbs pancreatic cancer progression.Nature communications · 2023Article
- Review
- Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers.Bioengineering (Basel, Switzerland) · 2023Article
- Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer.Cancer letters · 2023Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal neoplasms, is characterized by an expanded stroma with marked fibrosis (desmoplasia). We previously generated pancreas epithelium-specific TGF-β receptor type II (Tgfbr2) knockout mice in the context of Kras activation (mice referred to herein as Kras+Tgfbr2KO mice) and found that they developed aggressive PDAC that recapitulated the histological manifestations of the human disease. The mouse PDAC tissue showed strong expression of connective tissue growth factor (Ctgf), a profibrotic and tumor-promoting factor, especially in the tumor-stromal border area, suggesting an active tumor-stromal interaction. Here we show that the PDAC cells in Kras+Tgfbr2KO mice secreted much higher levels of several Cxc chemokines compared with mouse pancreatic intraepithelial neoplasia cells, which are preinvasive. The Cxc chemokines induced Ctgf expression in the pancreatic stromal fibroblasts, not in the PDAC cells themselves. Subcutaneous grafting studies revealed that the fibroblasts enhanced growth of PDAC cell allografts, which was attenuated by Cxcr2 inhibition. Moreover, treating the Kras+Tgfbr2KO mice with the CXCR2 inhibitor reduced tumor progression. The decreased tumor progression correlated with reduced Ctgf expression and angiogenesis and increased overall survival. Taken together, our data indicate that tumor-stromal interactions via a Cxcr2-dependent chemokine and Ctgf axis can regulate PDAC progression. Further, our results suggest that inhibiting tumor-stromal interactions might be a promising therapeutic strategy for PDAC.
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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.