Skip to main content
SpringerLink
Log in

High Expression of CX3CL1/CX3CR1 Axis Predicts a Poor Prognosis of Pancreatic Ductal Adenocarcinoma

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

CX3CL1 is a member of the chemokine family, and its receptor, CX3CR1, is expressed in pancreatic ductal adenocarcinoma. However, it is unclear whether there is a correlation between the expression of CX3CL1/CX3CR1 axis and the prognosis of patients with pancreatic ductal adenocarcinoma.

Methods

Tissue microarray and immunohistochemistry were used to study the expression of CX3CL1 and CX3CR1 in 105 specimens of pancreatic ductal adenocarcinoma. We analyzed a relationship between patients’ clinicopathological parameters and overall survival to the expression level of the CX3CL1/CX3CR1 axis using standard statistical analysis.

Results

The expression of CX3CL1 and CX3CR1 (77.1 and 66.7 %, respectively) was clearly increased in areas of malignancy compared with peritumoral areas. We did not find any correlation between CX3CL1 and CX3CR1 expression with clinical or pathological data. Patients’ overall survival was clearly worse with the combined high expression of CX3CL1 and CX3CR1. Patients with a high CX3CL1 expression tumor had a significantly shorter overall survival. High CX3CR1 expression was an independent negative prognosis factor.

Conclusion

We propose that the expression level of CX3CL1/CX3CR1 axis could provide clinical prognostic value, and the next steps should be to further investigate the mechanism by which CX3CL1 and its receptor impact survival in pancreatic ductal adenocarcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics. 2007. CA Cancer J Clin. 2007; 57: 43–66.

    Article  PubMed  Google Scholar 

  2. Lillemoe KD, Yeo CJ, Cameron JL. Pancreatic cancer: State-of-the-art care. CA Cancer J Clin 2000; 50: 241-268.

    Article  PubMed  CAS  Google Scholar 

  3. Kleeff J, Friess H. Nonmetastatic pancreatic cancer: Many trials, little progress. J Clin Oncol. 2008; 26: 3100; author reply 3100–3101.

    Article  PubMed  Google Scholar 

  4. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ. A new class of membrane-bound chemokine with a CX3C motif. Nature. 1997; 385: 640–644.

    Article  PubMed  CAS  Google Scholar 

  5. Pan Y, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, Vath J, Gosselin M, Ma J, Dussault B, Woolf E, Alperin G, Culpepper J, Gutierrez-Ramos JC, Gearing D. Neurotactin, a membraneanchored chemokine upregulated in brain inflammation. Nature. 1997; 387: 611–617.

    Article  PubMed  CAS  Google Scholar 

  6. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 1997; 91: 521–530.

    Article  PubMed  CAS  Google Scholar 

  7. Premack BA, Schall TJ. Chemokine receptors: Gateways to inflammation and infection. Nat Med. 1996; 2: 1174–1178.

    Article  PubMed  CAS  Google Scholar 

  8. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000; 18: 217–242.

    Article  PubMed  CAS  Google Scholar 

  9. Ohta M, Tanaka F, Yamaguchi H, Sadanaga N, Inoue H, Mori M. The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. Int J Oncol. 2005; 26: 41–47.

    PubMed  CAS  Google Scholar 

  10. Shulby SA, Dolloff NG, Stearns ME, Meucci O, Fatatis A. CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion, migration, and survival of human prostate cancer cells. Cancer Res. 2004; 64: 4693–4698.

    Article  PubMed  CAS  Google Scholar 

  11. Hyakudomi M, Matsubara T, Hyakudomi R, Yamamoto T, Kinugasa S, Yamanoi A, Maruyama R, Tanaka T. Increased expression of fractalkine is correlated with a better prognosis and an increased number of both CD8+ T cells and natural killer cells in gastric adenocarcinoma. Ann Surg Oncol. 2008; 15: 1775–1782.

    Article  PubMed  Google Scholar 

  12. Marchesi F, Piemonti L, Fedele G, Destro A, Roncalli M, Albarello L, Doglioni C, Anselmo A, Doni A, Bianchi P, Laghi L, Malesci A, Cervo L, Malosio M, Reni M,Zerbi A, Di Carlo V, Mantovani A, Allavena P. The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma. Cancer Res. 2008; 68: 9060–9069.

    Article  PubMed  CAS  Google Scholar 

  13. D'Haese JG, Demir IE, Friess H, Ceyhan GO. Fractalkine/CX3CR1: Why a single chemokine-receptor duo bears a major and unique therapeutic potential. Expert Opin Ther Targets. 2010; 14: 207–219.

    Article  PubMed  Google Scholar 

  14. Hatori K, Nagai A, Heisel R, Ryu JK, Kim SU. Fractalkine and fractalkine receptors in human neurons and glial cells. J Neurosci Res. 2002; 69: 418–426.

    Article  PubMed  CAS  Google Scholar 

  15. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 2006; 9: 917–924.

    Article  PubMed  CAS  Google Scholar 

  16. Matsubara T, Ono T, Yamanoi A, Tachibana M, Nagasue N. Fractalkine-CX3CR1 axis regulates tumor cell cycle and deteriorates prognosis after radical resection for hepatocellular carcinoma. J Surg Oncol. 2007; 95: 241–249..

    Article  PubMed  CAS  Google Scholar 

  17. Andre F, Cabioglu N, Assi H, Sabourin JC, Delaloge S, Sahin A, Broglio K, Spano JP, Combadiere C, Bucana C, Soria JC, Cristofanilli M. Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol. 2006; 17: 945–951.

    Article  PubMed  CAS  Google Scholar 

  18. Harnden P, Shelley MD, Clements H, Coles B, Tyndale-Biscoe RS, Naylor B, Mason MD. The prognostic significance of perineural invasion in prostatic cancer biopsies: A systematic review. Cancer. 2007; 109: 13–24.

    Article  PubMed  Google Scholar 

  19. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: A review of the literature. Cancer. 2009; 115: 3379–3391.

    Article  PubMed  CAS  Google Scholar 

  20. Vrielinck LJ, Ostyn F, van Damme B, van den Bogaert W, Fossion E. The significance of perinerual spread in adenoid cystic carcinoma of the major and minor salivary glands. Int J Oral Maxillofac Surg. 1988; 17: 190-193.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang S, Qi L, Li M, Zhang D, Xu S, Wang N, Sun B. Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer. J Exp Clin Cancer Res. 2008; 27: 62.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the patients who willingly and generously provided data and samples for research purposes and also appreciate the language polishing of Dr. Chaoling Yang and Dr. Shaunessy Rogers and the technical assistance of Ling Huang, Jun Lv, and Jingjing Xu.

Author information

Authors and Affiliations

  1. Department of Pancreatic Surgery, Chang Hai Hospital, The 2nd Millitary Medical University, Chang Hai Road No.168, Shanghai, 200433, China

    Xianhui Xu, Jinshui Chen, Hongyun Ma, Zhuo Shao & Gang Jin

  2. Department of Pathology, Chang Hai Hospital, The 2nd Millitary Medical University, Shanghai, China

    Yang Wang

  3. Department of Gastroenterology, Chang Hai Hospital, The 2nd Millitary Medical University, Shanghai, China

    Haitao Chen

Authors
  1. Xianhui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinshui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongyun Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhuo Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haitao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gang Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gang Jin.

Additional information

Xianhui Xu and Yang Wang contributed equally to this paper and wrote the paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, X., Wang, Y., Chen, J. et al. High Expression of CX3CL1/CX3CR1 Axis Predicts a Poor Prognosis of Pancreatic Ductal Adenocarcinoma. J Gastrointest Surg 16, 1493–1498 (2012). https://doi.org/10.1007/s11605-012-1921-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-012-1921-7

Keywords

Search

Navigation