ArticleBMC cancer2016
Enhancement of the CXCL12/CXCR4 axis due to acquisition of gemcitabine resistance in pancreatic cancer: effect of CXCR4 antagonists.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Kaempferol Inhibits MMP-1-Mediated Migration and Invasion in Gemcitabine-Resistant Pancreatic Cancer Cells.Nutrients · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Unveiling WHIM syndrome: Mavorixafor's emerging role in immune restoration and therapy.Clinical and experimental immunology · 2025Review
- Article
- The Role of Chemokines in Orchestrating the Immune Response to Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Deletion of the mRNA stability factorNAR cancer · 2023Article
- The role of CXCL12 axis in pancreatic cancer: New biomarkers and potential targets.Frontiers in oncology · 2023Review
- Therapeutic Perspectives of HIV-Associated Chemokine Receptor (CCR5 and CXCR4) Antagonists in Carcinomas.International journal of molecular sciences · 2022Review
- Regulation of pancreatic cancer therapy resistance by chemokines.Seminars in cancer biology · 2022Review
- Article
- Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2022Review
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- Enhanced CXCL12/CXCR4 signaling increases tumor progression in radiation‑resistant pancreatic cancer.Oncology reports · 2022Article
- A new era: tumor microenvironment in chemoresistance of pancreatic cancer.Journal of cancer science and clinical therapeutics · 2022Article
- CXCL12 secreted by pancreatic stellate cells accelerates gemcitabine resistance of pancreatic cancer by enhancing glycolytic reprogramming.Animal cells and systems · 2022Article
- Article
- Intraperitoneal siRNA Nanoparticles for Augmentation of Gemcitabine Efficacy in the Treatment of Pancreatic Cancer.Molecular pharmaceutics · 2021Article
- Review
- Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression.Frontiers in oncology · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe CXCL12-CXCR4 signaling axis in malignant tumor biology has increased in importance, and these peptides are implicated in tumor growth, invasion and metastasis. The aim of our study was to examine the important role of the axis in pancreatic cancer (PaCa) cells' relationship with stromal cells in gemcitabine-resistant (GEM-R) tumors and to confirm the effectiveness of CXCR4 antagonists for the treatment of GEM-R PaCa cells.
methodsWe established two GEM-R PaCa cell lines using MIA PaCa-2 and AsPC-1 cells. The expression of CXCR4 mRNA in PaCa cells and the expression of CXCL12 mRNA in fibroblasts were examined by reverse transcription polymerase chain reaction (RT-PCR). The expression of CXCR4 protein in PaCa cells was examined by immunosorbent assay (ELISA) and immunocytochemistry. Using Matrigel invasion assays and animal studies, we then examined the effects of two CXCR4 antagonists, AMD11070 and KRH3955, on the invasiveness and tumorigenicity of GEM-R PaCa cells stimulated by CXCL12.
resultsWe found that the expression of CXCR4 in GEM-R PaCa cells was significantly enhanced by GEM but not in normal GEM-sensitive (GEM-S) PaCa cells. In RT-PCR and ELISA assays, the production and secretion of CXCL12 from fibroblasts was significantly enhanced by co-culturing with GEM-R PaCa cells treated with GEM. In Matrigel invasion assays, the invasiveness of GEM-R PaCa cells treated with GEM was significantly activated by fibroblast-derived CXCL12 and was significantly inhibited by CXCR4 antagonists, AMD11070 and KRH3955. In vivo, the tumorigenicity of GEM-R PaCa cells was activated by GEM, and it was significantly inhibited by the addition with CXCR4 antagonists.
conclusionsOur findings demonstrate that the CXCL12-CXCR4 signaling axis plays an important role in PaCa cells' resistance to GEM. CXCR4 expression was significantly enhanced by the exposure to GEM in GEM-R PaCa cells but not in GEM-S PaCa cells. Furthermore, CXCR4 antagonists can inhibit the growth and invasion of GEM-R PaCa cells. These agents may be useful as second-line chemotherapy for GEM-R PaCa in the future.
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