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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
September 2012 Volume 4 Issue 3

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
September 2012 Volume 4 Issue 3

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

CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study

  • Authors:
    • Weixia Zhong
    • Weiwei Chen
    • Dexian Zhang
    • Jujie Sun
    • Yuhui Li
    • Jianbo Zhang
    • Yongsheng Gao
    • Wuyuan Zhou
    • Sheng Li
  • View Affiliations / Copyright

    Affiliations: Shandong Tumor Hospital, Jinan 250117, P.R. China, Jinan Central Hospital, Jinan 250001, P.R. China
  • Pages: 363-369
    |
    Published online on: July 4, 2012
       https://doi.org/10.3892/etm.2012.631
  • 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

Pancreatic cancer is one of the most lethal types of cancer, and curative resection is only applicable to potentially limited cases due to early metastasis and local invasion. This study reports the influence of CXCL12 and its receptor CXCR4 on the progression of pancreatic cancer and highlights the correlation between the CXCL12/CXCR4 axis and the organ-specific metastasis of pancreatic adenocarcinoma (PAC). A total of 34 patients with pancreatic cancer participated in the current study. The expression of CXCL12 and CXCR4 in cancerous tissues, paracancerous tissues, normal pancreas and lymph nodes surrounding the pancreas were investigated using immunohistochemistry and RT-PCR; furthermore, their relationship with clinicopathological factors was explored (PV9000 method). The positive rate of CXCL12 protein was 13.3% (4/30), the positive rate of CXCR4 protein was 80% (24/30) in tumor tissues. Additionally, a significant correlation between the expression pattern of the CXCL12/CXCR4 axis with lymph node metastasis was identified (P<0.05), excluding gender, age, tumor node metastasis (TNM) stage and differentiation (all P>0.05). Also, the positive rate of CXCL12 protein was 50% (15/30), the positive rate of CXCR4 protein was 73.3% (22/30) in the lymphocytes in lymph nodes surrounding the pancreas. Furthermore, we found that CXCL12 and CXCR4 expression in paratumorous vessels and neural tissue were significantly strongly positive. The paratumorous vessels and neural tissue with positive CXCL12 and CXCR4 expression were invaded by CXCL12-positive pancreatic cancer cells. The chemotactic interaction between CXCR4 and its ligand CXCL12 may be a critical event during the progression of pancreatic cancer. The CXCL12/CXCR4 axis plays an important role in the progression and organ-specific metastasis of pancreatic adenocarcinoma.
View Figures

Figure 1

Figure 2

Figure 3

View References

1. 

Oh JW, Olman M and Benveniste EN: CXCL12-mediated induction of plasminogen activator inhibitor-1 expression in human CXCR4-positive astroglioma cells. Biol Pharm Bull. 32:573–577. 2009. View Article : Google Scholar : PubMed/NCBI

2. 

Sallusto F, Mackay CR and Lanzavecchia A: The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol. 18:593–620. 2000. View Article : Google Scholar : PubMed/NCBI

3. 

Birk D, Fortnagel G, Formentini A and Beger HG: Small carcinoma of the pancreas. Factors of prognostic relevance. J Hepatobiliary Pancreat Surg. 5:450–454. 1998. View Article : Google Scholar : PubMed/NCBI

4. 

Salmaggi A, Maderna E, Calatozzolo C, et al: CXCL12, CXCR4 and CXCR7 expression in brain metastases. Cancer Biol Ther. 8:1608–1614. 2009. View Article : Google Scholar : PubMed/NCBI

5. 

Hassan S, Ferrario C, Saragovi U, et al: The influence of tumor-host interactions in the stromal cell-derived factor-1/CXCR4 ligand/receptor axis in determining metastatic risk in breast cancer. Am J Pathol. 175:66–73. 2009. View Article : Google Scholar : PubMed/NCBI

6. 

Welch DR and Goldberg SF: Molecular mechanisms controlling human melanoma progression and metastasis. Pathobiology. 65:311–330. 1997. View Article : Google Scholar : PubMed/NCBI

7. 

Lu C and Kerbel RS: Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J Cell Biol. 120:1281–1288. 1993.PubMed/NCBI

8. 

Wu X, Lee VC, Chevalier E and Hwang ST: Chemokine receptors as targets for cancer therapy. Curr Pharm Des. 15:742–757. 2009. View Article : Google Scholar : PubMed/NCBI

9. 

Kato M, Kitayama J, Kazama S and Nagawa H: Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma. Breast Cancer Res. 5:R144–150. 2003. View Article : Google Scholar : PubMed/NCBI

10. 

Liang Z, Brooks J, Willard M, Liang K, Yoon Y, Kang S and Shim H: CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway. Biochem Biophys Res Commun. 359:716–722. 2007. View Article : Google Scholar : PubMed/NCBI

11. 

Morales J, Homey B, Vicari AP, et al: CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells. Proc Natl Acad Sci USA. 96:14470–14475. 1999. View Article : Google Scholar : PubMed/NCBI

12. 

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

13. 

Campbell JJ and Butcher EC: Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol. 12:336–341. 2000. View Article : Google Scholar : PubMed/NCBI

14. 

Butcher EC, Williams M, Youngman K, Rott L and Briskin M: Lymphocyte trafficking and regional immunity. Adv Immunol. 72:209–253. 1999. View Article : Google Scholar : PubMed/NCBI

15. 

Klein RS, Rubin JB, Gibson HD, et al: SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development. 128:1971–1981. 2001.PubMed/NCBI

16. 

Peled A, Petit I, Kollet O, et al: Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 283:845–848. 1999. View Article : Google Scholar : PubMed/NCBI

17. 

Eash KJ, Means JM, White DW and Link DC: CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood. 113:4711–4719. 2009. View Article : Google Scholar : PubMed/NCBI

18. 

Salogni L, Musso T, Bosisio D, et al: Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. Blood. 113:5848–5856. 2009. View Article : Google Scholar : PubMed/NCBI

19. 

Monterrubio M, Mellado M, Carrera AC and Rodriguez-Frade JM: PI3Kgamma activation by CXCL12 regulates tumor cell adhesion and invasion. Biochem Biophys Res Commun. 388:199–204. 2009. View Article : Google Scholar : PubMed/NCBI

20. 

Sozzani S, Allavena P, D’Amico G, et al: Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. J Immunol. 161:1083–1086. 1998.PubMed/NCBI

21. 

Bottazzi B, Walter S, Govoni D, Colotta F and Mantovani A: Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma. J Immunol. 148:1280–1285. 1992.

22. 

Seo KS, Park JY, Davis WC, et al: Superantigen-mediated differentiation of bovine monocytes into dendritic cells. J Leukoc Biol. 85:606–616. 2009. View Article : Google Scholar : PubMed/NCBI

23. 

Leng Q, Nie Y, Zou Y and Chen J: Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development. BMC Immunol. 9:512008. View Article : Google Scholar : PubMed/NCBI

24. 

Sasaki K, Natsugoe S, Ishigami S, et al: Expression of CXCL12 and its receptor CXCR4 in esophageal squamous cell carcinoma. Oncol Rep. 21:65–71. 2009.PubMed/NCBI

25. 

Xu Q, Yuan X, Xu M, et al: Chemokine CXC receptor 4-mediated glioma tumor tracking by bone marrow – derived neural progenitor/stem cells. Mol Cancer Ther. 8:2746–2753. 2009.PubMed/NCBI

26. 

Uchida D, Onoue T, Begum NM, et al: Vesnarinone downregulates CXCR4 expression via upregulation of Kruppel-like factor 2 in oral cancer cells. Mol Cancer. 8:622009. View Article : Google Scholar : PubMed/NCBI

27. 

Mirisola V, Zuccarino A, Bachmeier BE, et al: CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival. Eur J Cancer. 45:2579–2587. 2009. View Article : Google Scholar : PubMed/NCBI

28. 

Sauter ER and Herlyn M: Molecular biology of human melanoma development and progression. Mol Carcinog. 23:132–143. 1998. View Article : Google Scholar : PubMed/NCBI

29. 

Vandercappellen J, Van Damme J and Struyf S: The role of CXC chemokines and their receptors in cancer. Cancer Lett. 267:226–244. 2008. View Article : Google Scholar : PubMed/NCBI

30. 

Wendt MK, Johanesen PA, Kang-Decker N, Binion DG, Shah V and Dwinell MB: Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis. Oncogene. 25:4986–4997. 2006. View Article : Google Scholar : PubMed/NCBI

31. 

Kucia M, Jankowski K, Reca R, et al: CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol. 35:233–245. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhong W, Chen W, Zhang D, Sun J, Li Y, Zhang J, Gao Y, Zhou W and Li S: CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study. Exp Ther Med 4: 363-369, 2012.
APA
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J. ... Li, S. (2012). CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study. Experimental and Therapeutic Medicine, 4, 363-369. https://doi.org/10.3892/etm.2012.631
MLA
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J., Gao, Y., Zhou, W., Li, S."CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study". Experimental and Therapeutic Medicine 4.3 (2012): 363-369.
Chicago
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J., Gao, Y., Zhou, W., Li, S."CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study". Experimental and Therapeutic Medicine 4, no. 3 (2012): 363-369. https://doi.org/10.3892/etm.2012.631
Copy and paste a formatted citation
x
Spandidos Publications style
Zhong W, Chen W, Zhang D, Sun J, Li Y, Zhang J, Gao Y, Zhou W and Li S: CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study. Exp Ther Med 4: 363-369, 2012.
APA
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J. ... Li, S. (2012). CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study. Experimental and Therapeutic Medicine, 4, 363-369. https://doi.org/10.3892/etm.2012.631
MLA
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J., Gao, Y., Zhou, W., Li, S."CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study". Experimental and Therapeutic Medicine 4.3 (2012): 363-369.
Chicago
Zhong, W., Chen, W., Zhang, D., Sun, J., Li, Y., Zhang, J., Gao, Y., Zhou, W., Li, S."CXCL12/CXCR4 axis plays pivotal roles in the organ-specific metastasis of pancreatic adenocarcinoma: A clinical study". Experimental and Therapeutic Medicine 4, no. 3 (2012): 363-369. https://doi.org/10.3892/etm.2012.631
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