ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
CXCR2 signaling promotes secretory cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- Cancer-associated fibroblast heterogeneity and its role in reshaping immunotherapy in solid cancers: potential strategies and clinical promise.Frontiers in cell and developmental biology · 2026Review
- Neutrophil Dynamics Contribute to Disease Progression and Poor Survival in Pancreatic Cancer.Cancers · 2025Article
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Innate Immunity and Platelets: Unveiling Their Role in Chronic Pancreatitis and Pancreatic Cancer.Cancers · 2025Review
- Modulating the CXCR2 Signaling Axis Using Engineered Chemokine Fusion Proteins to Disrupt Myeloid Cell Infiltration in Pancreatic Cancer.Biomolecules · 2025Article
- Article
- Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- The multi-faceted roles of cancer-associated fibroblasts in pancreatic cancer.Cellular signalling · 2025Review
- Article
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.Signal transduction and targeted therapy · 2024Review
- Article
- Cancer-associated fibroblasts: heterogeneity and their role in the tumor immune response.Clinical and experimental medicine · 2024Review
- Unveiling the immunosuppressive landscape of pancreatic ductal adenocarcinoma: implications for innovative immunotherapy strategies.Frontiers in oncology · 2024Review
- Fibroblasts and mouse breast cancer cells can form cellular aggregates in improved soft agar culture medium.Molecular and cellular biochemistry · 2023Article
- Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer.Cancer letters · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies. Desmoplasia and tumor-supporting inflammation are hallmarks of PDAC. The tumor microenvironment contributes significantly to tumor progression and spread. Cancer-associated fibroblasts (CAFs) facilitate therapy resistance and metastasis. Recent reports emphasized the concurrence of multiple subtypes of CAFs with diverse roles, fibrogenic, and secretory. C-X-C motif chemokine receptor 2 (CXCR2) is a chemokine receptor known for its role during inflammation and its adverse role in PDAC. Oncogenic Kras upregulates CXCR2 and its ligands and, thus, contribute to tumor proliferation and immunosuppression. CXCR2 deletion in a PDAC syngeneic mouse model produced increased fibrosis revealing a potential undescribed role of CXCR2 in CAFs. In this study, we demonstrate that the oncogenic Kras-CXCR2 axis regulates the CAFs function in PDAC and contributes to CAFs heterogeneity. We observed that oncogenic Kras and CXCR2 signaling alter CAFs, producing a secretory CAF phenotype with low fibrogenic features; and increased secretion of pro-tumor cytokines and CXCR2 ligands, utilizing the NF-κB activity. Finally, using syngeneic mouse models, we demonstrate that oncogenic Kras is associated with secretory CAFs and that CXCR2 inhibition promotes activation of fibrotic cells (myofibroblasts) and impact tumors in a mutation-dependent manner.
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Registered trials
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.