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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October 2013 Volume 6 Issue 4

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
October 2013 Volume 6 Issue 4

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

Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model

  • Authors:
    • Kang Su Cho
    • So Jung Yoon
    • Joo Yong Lee
    • Nam Hoon Cho
    • Young Deuk Choi
    • Yun Seob Song
    • Sung Joon Hong
  • View Affiliations / Copyright

    Affiliations: Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, Department of Urology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul 140-743, Republic of Korea
  • Pages: 933-938
    |
    Published online on: August 6, 2013
       https://doi.org/10.3892/ol.2013.1515
  • 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 stromal derived factor‑1 (SDF‑1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF‑1 and a CXCR4‑specific antagonist, AMD3100, on human prostate cancer PC‑3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC‑3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100‑treated and untreated groups. Cell proliferation was not significantly affected by SDF‑1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF‑1 stimulation enhanced the expression of phosphorylated Akt in the PC‑3 cells, but that the SDF‑1‑induced expression of phosphorylated Akt was abrogated in the AMD3100‑treated PC‑3 cells. In the PC‑3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100‑treated PC‑3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki‑67 and the anti‑apoptotic marker Bcl‑2 compared to control tumors in vivo. The CXCR4‑specific antagonist inhibits SDF‑1‑induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC‑3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration‑resistant prostate cancer (CRPC).
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

No authors listed. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The Leuprolide Study Group. N Engl J Med. 311:1281–1286. 1984. View Article : Google Scholar : PubMed/NCBI

2 

Gittes RF: Carcinoma of the prostate. N Engl J Med. 324:236–245. 1991. View Article : Google Scholar

3 

Wirth MP: Hormone-refractory prostate cancer: what have we learned? BJU Int. 100(Suppl 2): 56–59. 2007. View Article : Google Scholar

4 

Tashiro K, Tada H, Heilker R, Shirozu M, Nakano T and Honjo T: Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science. 261:600–603. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A and Springer TA: A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med. 184:1101–1109. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Wells TN, Power CA, Lusti-Narasimhan M, et al: Selectivity and antagonism of chemokine receptors. J Leukoc Biol. 59:53–60. 1996.PubMed/NCBI

7 

Zlotnik A: Chemokines and cancer. Int J Cancer. 119:2026–2029. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Balkwill F: The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 14:171–179. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Furusato B, Mohamed A, Uhlen M and Rhim JS: CXCR4 and cancer. Pathol Int. 60:497–505. 2010. View Article : Google Scholar

10 

Sun YX, Wang J, Shelburne CE, et al: Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J Cell Biochem. 89:462–473. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Akashi T, Koizumi K, Tsuneyama K, Saiki I, Takano Y and Fuse H: Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Sci. 99:539–542. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Darash-Yahana M, Pikarsky E, Abramovitch R, et al: Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J. 18:1240–1242. 2004.PubMed/NCBI

13 

Smart EJ and Anderson RG: Alterations in membrane cholesterol that affect structure and function of caveolae. Methods Enzymol. 353:131–139. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Kucia M, Reca R, Miekus K, et al: Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells. 23:879–894. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Wang J, Wang J, Sun Y, et al: Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis. Cell Signal. 17:1578–1592. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Chinni SR, Sivalogan S, Dong Z, et al: CXCL12/CXCR4 signaling activates Akt-1 and MMP-9 expression in prostate cancer cells: the role of bone microenvironment-associated CXCL12. Prostate. 66:32–48. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Singh S, Singh UP, Grizzle WE and Lillard JW Jr: CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest. 84:1666–1676. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Kukreja P, Abdel-Mageed AB, Mondal D, Liu K and Agrawal KC: Up-regulation of CXCR4 expression in PC-3 cells by stromal-derived factor-1alpha (CXCL12) increases endothelial adhesion and transendothelial migration: role of MEK/ERK signaling pathway-dependent NF-kappaB activation. Cancer Res. 65:9891–9898. 2005. View Article : Google Scholar

19 

Okera M, Bae K, Bernstein E, et al: Evaluation of nuclear factor kappaB and chemokine receptor CXCR4 co-expression in patients with prostate cancer in the Radiation Therapy Oncology Group (RTOG) 8610. BJU Int. 108:E51–E58. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Wang Q, Diao X, Sun J and Chen Z: Regulation of VEGF, MMP-9 and metastasis by CXCR4 in a prostate cancer cell line. Cell Biol Int. 35:897–904. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Leelawat K, Leelawat S, Narong S and Hongeng S: Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion. World J Gastroenterol. 13:1561–1568. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Libura J, Drukala J, Majka M, et al: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood. 100:2597–2606. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Mori T, Doi R, Koizumi M, et al: CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol Cancer Ther. 3:29–37. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Hong X, Jiang F, Kalkanis SN, et al: SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion. Cancer Lett. 236:39–45. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Gilbert DC, Chandler I, McIntyre A, et al: Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents. J Pathol. 217:94–102. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Kijima T, Maulik G, Ma PC, et al: Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. Cancer Res. 62:6304–6311. 2002.PubMed/NCBI

27 

Li JK, Yu L, Shen Y, Zhou LS, Wang YC and Zhang JH: Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro. World J Gastroenterol. 14:2308–2313. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Kajiyama H, Shibata K, Terauchi M, Ino K, Nawa A and Kikkawa F: Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. Int J Cancer. 122:91–99. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Sehgal A, Keener C, Boynton AL, Warrick J and Murphy GP: CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells. J Surg Oncol. 69:99–104. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Sehgal A, Ricks S, Boynton AL, Warrick J and Murphy GP: Molecular characterization of CXCR-4: a potential brain tumor-associated gene. J Surg Oncol. 69:239–248. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Uchida D, Onoue T, Tomizuka Y, et al: Involvement of an autocrine stromal cell derived factor-1/CXCR4 system on the distant metastasis of human oral squamous cell carcinoma. Mol Cancer Res. 5:685–694. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Kreisberg JI, Malik SN, Prihoda TJ, et al: Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Res. 64:5232–5236. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Ayala G, Thompson T, Yang G, et al: High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence. Clin Cancer Res. 10:6572–6578. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Rubin JB, Kung AL, Klein RS, et al: A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci USA. 100:13513–13518. 2003. View Article : Google Scholar : PubMed/NCBI

35 

De Falco V, Guarino V, Avilla E, et al: Biological role and potential therapeutic targeting of the chemokine receptor CXCR4 in undifferentiated thyroid cancer. Cancer Res. 67:11821–11829. 2007.PubMed/NCBI

36 

Yoon Y, Liang Z, Zhang X, et al: CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models. Cancer Res. 67:7518–7524. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Orimo A, Gupta PB, Sgroi DC, et al: Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 121:335–348. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Hendrix CW, Collier AC, Lederman MM, et al: Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr. 37:1253–1262. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cho KS, Yoon SJ, Lee JY, Cho NH, Choi YD, Song YS and Hong SJ: Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model. Oncol Lett 6: 933-938, 2013.
APA
Cho, K.S., Yoon, S.J., Lee, J.Y., Cho, N.H., Choi, Y.D., Song, Y.S., & Hong, S.J. (2013). Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model. Oncology Letters, 6, 933-938. https://doi.org/10.3892/ol.2013.1515
MLA
Cho, K. S., Yoon, S. J., Lee, J. Y., Cho, N. H., Choi, Y. D., Song, Y. S., Hong, S. J."Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model". Oncology Letters 6.4 (2013): 933-938.
Chicago
Cho, K. S., Yoon, S. J., Lee, J. Y., Cho, N. H., Choi, Y. D., Song, Y. S., Hong, S. J."Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model". Oncology Letters 6, no. 4 (2013): 933-938. https://doi.org/10.3892/ol.2013.1515
Copy and paste a formatted citation
x
Spandidos Publications style
Cho KS, Yoon SJ, Lee JY, Cho NH, Choi YD, Song YS and Hong SJ: Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model. Oncol Lett 6: 933-938, 2013.
APA
Cho, K.S., Yoon, S.J., Lee, J.Y., Cho, N.H., Choi, Y.D., Song, Y.S., & Hong, S.J. (2013). Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model. Oncology Letters, 6, 933-938. https://doi.org/10.3892/ol.2013.1515
MLA
Cho, K. S., Yoon, S. J., Lee, J. Y., Cho, N. H., Choi, Y. D., Song, Y. S., Hong, S. J."Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model". Oncology Letters 6.4 (2013): 933-938.
Chicago
Cho, K. S., Yoon, S. J., Lee, J. Y., Cho, N. H., Choi, Y. D., Song, Y. S., Hong, S. J."Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model". Oncology Letters 6, no. 4 (2013): 933-938. https://doi.org/10.3892/ol.2013.1515
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