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Original Articles
CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer
Guolin Zhang, Xin Luo, Wei Zhang, Engeng Chen, Jianbin Xu, Fei Wang, Gaoyang Cao, Zhenyu Ju, Dongai Jin, Xuefeng Huang, Wei Zhou, Zhangfa Song
Cancer Res Treat. 2020;52(2):622-633.   Published online December 31, 2019
DOI: https://doi.org/10.4143/crt.2019.593
AbstractAbstract PDFPubReaderePub
Purpose
5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu.
Materials and Methods
CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.
Results
In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13.
Conclusion
These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatment strategies.

Citations

Citations to this article as recorded by  
  • Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance
    Hongxin HE, Shiyao ZHENG, Shangkun JIN, Weijie HUANG, Enhao WEI, Shen GUAN, Chunkang YANG
    Scientific Reports.2025;[Epub]     CrossRef
  • Mechanism of 5-fluorouracil induced resistance and role of piperine and curcumin as chemo-sensitizers in colon cancer
    Dorothy Bhattacharjya, Nageswaran Sivalingam
    Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(11): 8445.     CrossRef
  • The combination of SHP099 inhibits the malignant biological behavior of L-OHP/5-FU-resistant colorectal cancer cells by regulating energy metabolism reprogramming
    Meilian Wang, Kun Yu, Wen Fu, Lihong Yang
    Biochemical and Biophysical Research Communications.2024; 728: 150262.     CrossRef
  • Serum CXCL13 as a Novel Biomarker in Oral Squamous Cell Carcinoma
    Shin Tojo, Koh‐ichi Nakashiro, Nobuyuki Kuribayashi, Daisuke Uchida
    Cancer Medicine.2024;[Epub]     CrossRef
  • The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights
    Xunxing Hao, Meng Ding, Chenyu Chi, Xiaodong Xu, Xiaoyu Zhang, Mingzhe Hu
    Discover Oncology.2024;[Epub]     CrossRef
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    Jiazheng Li, Chao Yang, Yongbin Zheng
    Frontiers in Genetics.2023;[Epub]     CrossRef
  • Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer
    Cairu Gu, Xifeng Xiong, Wei Liu, Elisa Belluzzi
    Disease Markers.2023; 2023: 1.     CrossRef
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    Yaoqing Li, Chuchu Xu, Renjun Zhu, Liyijing Shen, Gengyuan Hu, Kelong Tao, Feng Tao, Zengxin Lu, Guolin Zhang
    Journal of Cancer Research and Clinical Oncology.2023; 149(10): 7235.     CrossRef
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    International Journal of Molecular Sciences.2023; 24(23): 16638.     CrossRef
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    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Identification of Key Gene Targets for Sensitizing Colorectal Cancer to Chemoradiation: an Integrative Network Analysis on Multiple Transcriptomics Data
    Hamed Manoochehri, Akram Jalali, Hamid Tanzadehpanah, Amir Taherkhani, Massoud Saidijam
    Journal of Gastrointestinal Cancer.2022; 53(3): 649.     CrossRef
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    Na Xu, Ranran Guo, Xiaotong Yang, Ning Li, Jia Yu, Peng Zhang
    Asian Journal of Pharmaceutical Sciences.2022; 17(3): 385.     CrossRef
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    Ching-Hung Hsieh, Cheng-Zhe Jian, Liang-In Lin, Guan-Sian Low, Ping-Yun Ou, Chiun Hsu, Da-Liang Ou
    Cancers.2022; 14(2): 294.     CrossRef
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    Xiaonan Zhou, Shizhu Guo, Yonghong Shi
    Scientific Reports.2022;[Epub]     CrossRef
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    Haili Wu, Jin’e Du, Chenglu Li, Hanqing Li, Huiqin Guo, Zhuoyu Li
    International Journal of Molecular Sciences.2022; 23(7): 3544.     CrossRef
  • Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact
    Maria Braoudaki, Mohammed Saqif Ahmad, Denis Mustafov, Sara Seriah, Mohammad Naseem Siddiqui, Shoib Sarwar Siddiqui
    Seminars in Cancer Biology.2022; 86: 436.     CrossRef
  • Bioinformatics Analysis of Prognostic Significance and Immune Characteristics of CXC Chemokine Family in Patients with Lung Adenocarcinoma
    Dachen Bian, Yanhua Chen, Ahmed Faeq Hussein
    Computational and Mathematical Methods in Medicine.2022; 2022: 1.     CrossRef
  • Chemokines in progression, chemoresistance, diagnosis, and prognosis of colorectal cancer
    Qian Zou, Xue Lei, Aijing Xu, Ziqi Li, Qinglian He, Xiujuan Huang, Guangxian Xu, Faqing Tian, Yuanlin Ding, Wei Zhu
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    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2022; 1877(5): 188799.     CrossRef
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  • Identification of necroptosis-related subtypes, development of a novel signature, and characterization of immune infiltration in colorectal cancer
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  • Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment
    Shamin Azwar, Heng Fong Seow, Maha Abdullah, Mohd Faisal Jabar, Norhafizah Mohtarrudin
    Biology.2021; 10(9): 854.     CrossRef
  • CXCL2-mediated ATR/CHK1 signaling pathway and platinum resistance in epithelial ovarian cancer
    Sipei Nie, Yicong Wan, Hui Wang, Jinhui Liu, Jing Yang, Rui Sun, Huangyang Meng, Xiaolin Ma, Yi Jiang, Wenjun Cheng
    Journal of Ovarian Research.2021;[Epub]     CrossRef
  • The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
    Zeyu Wang, Yuze Liu, Yuyao Mo, Hao Zhang, Ziyu Dai, Xun Zhang, Weijie Ye, Hui Cao, Zhixiong Liu, Quan Cheng
    Frontiers in Immunology.2021;[Epub]     CrossRef
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    Louis Boafo Kwantwi, Shujing Wang, Youjing Sheng, Qiang Wu
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  • CXCL13 in Cancer and Other Diseases: Biological Functions, Clinical Significance, and Therapeutic Opportunities
    San-Hui Gao, Sheng-Zhi Liu, Gui-Zhen Wang, Guang-Biao Zhou
    Life.2021; 11(12): 1282.     CrossRef
  • Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment
    Margarita Neganova, Junqi Liu, Yulia Aleksandrova, Sergey Klochkov, Ruitai Fan
    Cancers.2021; 13(23): 6062.     CrossRef
  • Chemoresistance Mechanisms in Colon Cancer: Focus on Conventional Chemotherapy
    Klara Mladenić , Mirela Sedić
    Clinical Cancer Drugs.2021; 8(2): 67.     CrossRef
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  • 29 Web of Science
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CCL2 Chemokine as a Potential Biomarker for Prostate Cancer: A Pilot Study
Igor Tsaur, Anika Noack, Jasmina Makarevic, Elsie Oppermann, Ana Maria Waaga-Gasser, Martin Gasser, Hendrik Borgmann, Tanja Huesch, Kilian M. Gust, Michael Reiter, David Schilling, Georg Bartsch, Axel Haferkamp, Roman A. Blaheta
Cancer Res Treat. 2015;47(2):306-312.   Published online October 13, 2014
DOI: https://doi.org/10.4143/crt.2014.015
AbstractAbstract PDFPubReaderePub
Purpose
Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa. Materials and Methods Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested. Results The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading. Conclusion Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.

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