Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
February-2015 Volume 33 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2015 Volume 33 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer

  • Authors:
    • Lu-Min Wei
    • Shan Cao
    • Wei-Dong Yu
    • Yu-Lan Liu
    • Jing-Tong Wang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, P.R. China
  • Pages: 615-624
    |
    Published online on: December 4, 2014
       https://doi.org/10.3892/or.2014.3645
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The CX3CR1/CX3CL1 axis is involved in the metastasis and prognosis of many types of cancer; however, whether CX3CR1 is expressed in gastric cancer cells and whether it participates in gastric cancer metastasis remain unknown. We investigated the expression of CX3CR1 in gastric cancer tissues and non‑neoplastic gastric tissues in vivo and in gastric cancer cell lines and a gastric epithelial cell line in vitro, and then the functional roles of CX3CR1 in cellular metastasis, proliferation and survival were explored. We observed that CX3CR1 was highly expressed in gastric cancer tissues in vivo and was related to lymph node metastasis, higher clinical TNM stage and larger tumor size. In vitro, CX3CR1 overexpression promoted gastric cancer cell migration, invasion, proliferation and survival. Additionally, different from several chemokine receptors, CX3CR1 was also expressed in non-neoplastic gastric tissues and in gastric epithelial cells and played a functional role in vitro. Notably, gastric cancer tissues expressed higher CX3CR1 compared with that in the non-neoplastic gastric tissues in vivo, while in vitro, CX3CR1 expresssion in the gastric cancer cell lines was equivalent or significantly lower than that in the gastric epithelial cell line, which suggests that the high expression of CX3CR1 in gastric cancer in vivo might be induced, not constitutive. Altogether, our findings suggest that on the one hand overexpression of CX3CR1 promoted gastric cancer metastasis, proliferation and survival; on the other hand, appropriate expression of CX3CR1 in normal gastric tissues may play a physiological role in tissue remodeling after injury and/or epithelial renewal. Additionally, the tumor microenvironment may play an important role in the high expression of CX3CR1 in gastric cancer cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Brenner H, Rothenbacher D and Arndt V: Epidemiology of stomach cancer. Methods Mol Biol. 472:467–477. 2009. View Article : Google Scholar

2 

Herszenyi L and Tulassay Z: Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 14:249–258. 2010.PubMed/NCBI

3 

Hyung WJ, Noh SH, Yoo CH, et al: Prognostic significance of metastatic lymph node ratio in T3 gastric cancer. World J Surg. 26:323–329. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Feng J, Wu YF, Xu HM, Wang SB and Chen JQ: Prognostic significance of the metastatic lymph node ratio in T3 gastric cancer patients undergoing total gastrectomy. Asian Pac J Cancer Prev. 12:3289–3292. 2011.PubMed/NCBI

5 

Zlotnik A and Yoshie O: Chemokines: a new classification system and their role in immunity. Immunity. 12:121–127. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Balkwill F: Cancer and the chemokine network. Nat Rev Cancer. 4:540–550. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Zlotnik A: Chemokines in neoplastic progression. Semin Cancer Biol. 14:181–185. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Righi E, Kashiwagi S, Yuan J, et al: CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res. 71:5522–5534. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Marchesi F, Grizzi F, Laghi L, Mantovani A and Allavena P: Molecular mechanisms of pancreatic cancer dissemination: the role of the chemokine system. Curr Pharm Des. 18:2432–2438. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Balkwill FR: The chemokine system and cancer. J Pathol. 226:148–157. 2012. View Article : Google Scholar

11 

Yao X, Qi L, Chen X, Du J, Zhang Z and Liu S: Expression of CX3CR1 associates with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma. Urol Oncol. 32:162–170. 2014. View Article : Google Scholar

12 

Wang WN, Chen Y, Zhang YD and Hu TH: The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer. Tumour Biol. 34:1865–1871. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Marchesi F, Piemonti L, Mantovani A and Allavena P: Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis. Cytokine Growth Factor Rev. 21:77–82. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Lee JH, Cho YS, Lee JY, et al: The chemokine receptor CCR4 is expressed and associated with a poor prognosis in patients with gastric cancer. Ann Surg. 249:933–941. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Jamieson WL, Shimizu S, D’Ambrosio JA, Meucci O and Fatatis A: CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res. 68:1715–1722. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Marchesi F, Piemonti L, Fedele G, et al: The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma. Cancer Res. 68:9060–9069. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Kodama J, Hasengaowa, Kusumoto T, et al: Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer. Ann Oncol. 18:70–76. 2007. View Article : Google Scholar

18 

Miao Z, Luker KE, Summers BC, et al: CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA. 104:15735–15740. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Andre F, Cabioglu N, Assi H, et al: Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol. 17:945–951. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Meijer J, Zeelenberg IS, Sipos B and Roos E: The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver. Cancer Res. 66:9576–9582. 2006. View Article : Google Scholar : PubMed/NCBI

21 

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

22 

Marchesi F, Monti P, Leone BE, et al: Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res. 64:8420–8427. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Mashino K, Sadanaga N, Yamaguchi H, et al: Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma. Cancer Res. 62:2937–2941. 2002.PubMed/NCBI

24 

Brand S, Sakaguchi T, Gu X, Colgan SP and Reinecker HC: Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells. Gastroenterology. 122:166–177. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Muller A, Homey B, Soto H, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature. 410:50–56. 2001. View Article : Google Scholar : PubMed/NCBI

26 

White GE and Greaves DR: Fractalkine: one chemokine, many functions. Blood. 113:767–768. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Bazan JF, Bacon KB, Hardiman G, et al: A new class of membrane-bound chemokine with a CX3C motif. Nature. 385:640–644. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Lucas AD, Chadwick N, Warren BF, et al: The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo. Am J Pathol. 158:855–866. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Hundhausen C, Misztela D, Berkhout TA, et al: The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 102:1186–1195. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Imai T, Hieshima K, Haskell C, et al: Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 91:521–530. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Nevo I, Sagi-Assif O, Meshel T, et al: The involvement of the fractalkine receptor in the transmigration of neuroblastoma cells through bone-marrow endothelial cells. Cancer Lett. 273:127–139. 2009. View Article : Google Scholar

32 

Locatelli M, Boiocchi L, Ferrero S, et al: Human glioma tumors express high levels of the chemokine receptor CX3CR1. Eur Cytokine Netw. 21:27–33. 2010.PubMed/NCBI

33 

Zhao BC, Wang ZJ, Mao WZ, et al: CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma. World J Gastroenterol. 17:2389–2396. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Meucci O, Fatatis A, Simen AA and Miller RJ: Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci USA. 97:8075–8080. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Alessi DR, Andjelkovic M, Caudwell B, et al: Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15:6541–6551. 1996.PubMed/NCBI

36 

Gaudin F, Nasreddine S, Donnadieu AC, et al: Identification of the chemokine CX3CL1 as a new regulator of malignant cell proliferation in epithelial ovarian cancer. PLoS One. 6:e215462011. View Article : Google Scholar : PubMed/NCBI

37 

Lee SJ, Namkoong S, Kim YM, et al: Fractalkine stimulates angiogenesis by activating the Raf-1/MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways. Am J Physiol Heart Circ Physiol. 291:H2836–H2846. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Ishigami S, Natsugoe S, Okumura H, et al: Clinical implication of CXCL12 expression in gastric cancer. Ann Surg Oncol. 14:3154–3158. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Murdoch C, Monk PN and Finn A: Functional expression of chemokine receptor CXCR4 on human epithelial cells. Immunology. 98:36–41. 1999. View Article : Google Scholar : PubMed/NCBI

40 

Banas B, Wornle M, Berger T, et al: Roles of SLC/CCL21 and CCR7 in human kidney for mesangial proliferation, migration, apoptosis, and tissue homeostasis. J Immunol. 168:4301–4307. 2002. View Article : Google Scholar : PubMed/NCBI

41 

Schutyser E, Su Y, Yu Y, et al: Hypoxia enhances CXCR4 expression in human microvascular endothelial cells and human melanoma cells. Eur Cytokine Netw. 18:59–70. 2007.PubMed/NCBI

42 

Ishikawa T, Nakashiro K, Klosek SK, et al: Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Rep. 21:707–712. 2009.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wei L, Cao S, Yu W, Liu Y and Wang J: Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer. Oncol Rep 33: 615-624, 2015.
APA
Wei, L., Cao, S., Yu, W., Liu, Y., & Wang, J. (2015). Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer. Oncology Reports, 33, 615-624. https://doi.org/10.3892/or.2014.3645
MLA
Wei, L., Cao, S., Yu, W., Liu, Y., Wang, J."Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer". Oncology Reports 33.2 (2015): 615-624.
Chicago
Wei, L., Cao, S., Yu, W., Liu, Y., Wang, J."Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer". Oncology Reports 33, no. 2 (2015): 615-624. https://doi.org/10.3892/or.2014.3645
Copy and paste a formatted citation
x
Spandidos Publications style
Wei L, Cao S, Yu W, Liu Y and Wang J: Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer. Oncol Rep 33: 615-624, 2015.
APA
Wei, L., Cao, S., Yu, W., Liu, Y., & Wang, J. (2015). Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer. Oncology Reports, 33, 615-624. https://doi.org/10.3892/or.2014.3645
MLA
Wei, L., Cao, S., Yu, W., Liu, Y., Wang, J."Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer". Oncology Reports 33.2 (2015): 615-624.
Chicago
Wei, L., Cao, S., Yu, W., Liu, Y., Wang, J."Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer". Oncology Reports 33, no. 2 (2015): 615-624. https://doi.org/10.3892/or.2014.3645
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team