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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
May 2013 Volume 31 Issue 5

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
May 2013 Volume 31 Issue 5

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

Potential implication of IL-24 in lymphangiogenesis of human breast cancer

  • Authors:
    • Natasha C. Frewer
    • Lin Ye
    • Ping-Hui Sun
    • Sioned Owen
    • Ke Ji
    • Kathryn A. Frewer
    • Rachel Hargest
    • Wen G. Jiang
  • View Affiliations / Copyright

    Affiliations: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
  • Pages: 1097-1104
    |
    Published online on: March 27, 2013
       https://doi.org/10.3892/ijmm.2013.1319
  • 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

Lymphangiogenesis is involved in the dissemination of malignant cells from solid tumours to regional lymph nodes and possibly to various distant sites. Lymphangiogenesis is regulated by vascular endothelial growth factor (VEGF)-C and VEGF-D. Interleukin (IL)-24 is known as a cytokine with potent antitumour and tumour-suppressive activity which functions through its receptor (IL-22R). Expression of IL-24 has been shown to be reduced in breast cancer, and the reduced expression is associated with lymphatic metastases and a poor prognosis. However, the involvement of IL-24 in lymphangiogenesis during lymphatic metastasis remains unclear. The aim of the present study was to determine whether there is an association between IL-24, IL-22R and lymphangiogenic factors and markers in breast cancer. Analysis of IL-24, IL-22R and lymphangiogenic factors in malignant breast tissue samples (n=127) revealed a correlation between increased expression of lymphangiogenic markers (podoplanin, Prox-1 and LYVE-1) and reduced levels of IL-24 and IL-22R. Samples stained with a high degree of positivity for lymphangiogenic factors and markers whereas staining for IL-24 was weak. In vitro assays showed that the average perimeter length of microtubules formed by endothelial cells treated with IL-24 was significantly reduced compared to the control. The growth of endothelial cells was significantly reduced when exposed to a high concentration of IL-24 (250 ng/ml). Treatment of HECV cells with IL-24 resulted in significantly reduced expression of VEGF-C (P<0.05) and VEGF-D (P<0.001). In conclusion, reduced expression of IL-24 and IL-22R in breast cancer is correlated with increased expression of specific lymphangiogenic markers. IL-24 suppressed in vitro growth and microtubule formation of endothelial cells. IL-24 may downregulate the expression of lymphangiogenic markers and factors although further research is required. This suggests that IL-24 plays a profound role in suppressing tumour lymphangiogenesis, thereby, reducing the likelihood of cancer metastasis via the lymphatic route.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K and Detmar M: Induction of tumour lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 7:192–198. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Al-Rawi MA and Jiang WG: Lymphangiogenesis and cancer metastasis. Front Biosci. 16:723–739. 2011. View Article : Google Scholar

3 

Weninger W, Partanen TA, Breiteneder-Geleff S, Mayer C, Kowalski H, Mildner M, Pammer J, Stürzl M, Kerjaschki D, Alitalo K and Tschachler E: Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi’s sarcoma tumor cells. Lab Invest. 79:243–251. 1999.PubMed/NCBI

4 

Wigle JT and Oliver G: Prox1 function is required for the development of the murine lymphatic system. Cell. 98:769–778. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DJ, Orc L, Alitalo K, Christofori G and Pepper MS: Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 20:672–682. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Choi WW, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, Cohen C and Young AN: Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol. 18:143–152. 2005. View Article : Google Scholar

7 

Lee SK, Cho EY, Kim WW, Kim S, Hur SM, Kim S, Choe JH, Kim JH, Kim JS, Lee JE, Nam SJ and Yang JH: The prediction of lymph node metastasis in ductal carcinoma in situ with microinvasion by assessing lymphangiogenesis. J Surg Oncol. 102:225–229. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Bono P, Wasenius VM, Heikkilä P, Lundin J, Jackson DG and Joensuu H: High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Cancer Res. 10:7144–7149. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Nakamura Y, Yasuoka H, Tsujimoto M, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I and Kakudo K: Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. Breast Cancer Res Treat. 91:125–132. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Stacker SA, Achen MG, Jussila L, Baldwin ME and Alitalo K: Lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2:573–583. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S and Sugimachi K: Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer. Breast Cancer Res Treat. 66:159–164. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Cunnick GH, Jiang WG, Douglas-Jones T, Watkins G, Gomez KF, Morgan MJ, Subramanian A, Mokbel K and Mansel RE: Lymphangiogenesis and lymph node metastasis in breast cancer. Mol Cancer. 7:232008. View Article : Google Scholar : PubMed/NCBI

13 

Weidner N: Tumour vascularity and proliferation: clear evidence of a close relationship. J Pathol. 189:297–299. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Van den Eynden GG, Van der Auwera I, Van Laere SJ, Huygelen V, Colpaert CG, van Dam P, Dirix LY, Vermeulen PB and Van Marck EA: Induction of lymphangiogenesis in and around axillary lymph node metastases of patients with breast cancer. Br J Cancer. 95:1362–1366. 2006.PubMed/NCBI

15 

Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, Kang D, Jiang H, Lin JJ, Alexandre D, Chen Y, Vozhilla N, Mei MX, Christiansen KA, Sivo F, Goldstein NI, Mhashikar AB, Chada S, Huberman E, Pestka S and Fisher PB: Genomic structure, chromosomal localisation and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene. 20:7051–7063. 2001. View Article : Google Scholar

16 

Dash R, Bhutia SK, Azab B, Su ZZ, Quinn BA, Kegelmen TP, Das SK, Kim K, Lee SG, Park MA, Yacoub A, Rahmani M, Emdad L, Dmitriev IP, Wang XY, Sarkar D, Grant S, Dent P, Curiel DT and Fisher PB: mda-7/IL/24: a unique member of the IL-10 gene family promoting cancer-targeted toxicity. Cytokine Growth Factor Rev. 21:381–391. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Ramesh R, Mhashilkar AM, Tanaka F, Saito Y, Branch CD, Sieger K, Mumm JB, Stewart AL, Boquoi A, Dumoutier L, Grimm EA, Renauld JC, Kotenko S and Chada S: Melanoma differentiation-associated gene7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer Res. 63:5105–5113. 2003.PubMed/NCBI

18 

Jiang H, Lin JJ, Su ZZ, Goldstein NI and Fisher PB: Subtract ion hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene. 11:2477–2486. 1995.

19 

Patani N, Douglas-Jones A, Mansel R, Jiang W and Mokbel K: Tumour suppressor function of MDA-7/IL-24 in human breast cancer. Cancer Cell Int. 10:292010.PubMed/NCBI

20 

Jiang WG, Douglas-Jones A and Mansel RE: Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, in human breast cancer correlates with clinical outcomes. Int J Cancer. 106:752–757. 2003. View Article : Google Scholar

21 

Al-Rawi MA, Watkins G, Mansel RE and Jiang WG: The effects of interleukin-7 on the lymphangiogenic properties of human endothelial cells. Int J Oncol. 27:721–730. 2005.PubMed/NCBI

22 

Jiang WG, Hiscox SE, Parr C, Martin TA, Matsumoto K, Nakamura T and Mansel RE: Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res. 5:3695–3703. 1999.

23 

Sanders AJ, Ye L, Mason MD and Jiang WG: The impact of EPLINα (epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis. Angiogenesis. 13:317–326. 2010.

24 

Jiang WG, Hiscox S, Hallett MB, Horrobin DF, Scott C and Puntis MCA: Inhibition of hepatocyte growth factor-induced motility and in vitro invasion of human colon cancer cells by gamma-linolenic acid. Br J Cancer. 71:744–752. 1995. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Frewer NC, Ye L, Sun P, Owen S, Ji K, Frewer KA, Hargest R and Jiang WG: Potential implication of IL-24 in lymphangiogenesis of human breast cancer. Int J Mol Med 31: 1097-1104, 2013.
APA
Frewer, N.C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K.A. ... Jiang, W.G. (2013). Potential implication of IL-24 in lymphangiogenesis of human breast cancer. International Journal of Molecular Medicine, 31, 1097-1104. https://doi.org/10.3892/ijmm.2013.1319
MLA
Frewer, N. C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K. A., Hargest, R., Jiang, W. G."Potential implication of IL-24 in lymphangiogenesis of human breast cancer". International Journal of Molecular Medicine 31.5 (2013): 1097-1104.
Chicago
Frewer, N. C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K. A., Hargest, R., Jiang, W. G."Potential implication of IL-24 in lymphangiogenesis of human breast cancer". International Journal of Molecular Medicine 31, no. 5 (2013): 1097-1104. https://doi.org/10.3892/ijmm.2013.1319
Copy and paste a formatted citation
x
Spandidos Publications style
Frewer NC, Ye L, Sun P, Owen S, Ji K, Frewer KA, Hargest R and Jiang WG: Potential implication of IL-24 in lymphangiogenesis of human breast cancer. Int J Mol Med 31: 1097-1104, 2013.
APA
Frewer, N.C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K.A. ... Jiang, W.G. (2013). Potential implication of IL-24 in lymphangiogenesis of human breast cancer. International Journal of Molecular Medicine, 31, 1097-1104. https://doi.org/10.3892/ijmm.2013.1319
MLA
Frewer, N. C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K. A., Hargest, R., Jiang, W. G."Potential implication of IL-24 in lymphangiogenesis of human breast cancer". International Journal of Molecular Medicine 31.5 (2013): 1097-1104.
Chicago
Frewer, N. C., Ye, L., Sun, P., Owen, S., Ji, K., Frewer, K. A., Hargest, R., Jiang, W. G."Potential implication of IL-24 in lymphangiogenesis of human breast cancer". International Journal of Molecular Medicine 31, no. 5 (2013): 1097-1104. https://doi.org/10.3892/ijmm.2013.1319
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