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
August-2015 Volume 34 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
August-2015 Volume 34 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

High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome

  • Authors:
    • Hong-Jun Li
    • Qi-Man Sun
    • Long-Zi Liu
    • Jun Zhang
    • Jun Huang
    • Cheng-Hong Wang
    • Rui Ding
    • Kang Song
    • Zhong Tong
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
  • Pages: 795-802
    |
    Published online on: June 15, 2015
       https://doi.org/10.3892/or.2015.4060
  • 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

Interleukin-9 receptor (IL-9R) overexpression has a pivotal role in human hematological malignancies. However, the expression of IL-9R and its biological role in human solid tumors remains elusive. In the present study, western blot analysis and RT-qPCR were used to determine the expression of IL-9R in hepatocellular carcinoma (HCC) cell lines and tumor tissues. Proliferation, cell cycle, apoptosis and Transwell assays were used to examine the biological role of IL-9R in HCC cells. The results showed that IL-9R and its ligand IL-9 were constitutively expressed in HCC cells and tissues. Moreover, the expression levels of IL-9R and IL-9 were significantly higher in tumor tissues compared to the peritumor liver tissues. Functional experiments suggested that IL-9R significantly promoted HCC cell proliferation, invasion and inhibited apoptosis, possibly by acting through the IL-9/IL-9R axis. After silencing IL-9R, the expression of VEGF, p-p38, p-STAT3 and MMP9, markedly decreased suggesting the potential involvement of these molecules in IL-9R activity. Immunohistochemistry‑based survival analysis revealed that a differential expression of IL-9R in HCC tissue was a significant and independent prognostic factor for survival [HR, 1.66; 95% confidence interval (CI), 1.17-2.36; P=0.005] and recurrence [HR, 1.50; 95%CI, 1.04‑2.17; P=0.03]. In addition, a high IL-9R expression positively and significantly correlated with larger (P=0.012) and advanced tumor stage (P=0.018). The findings indicated that IL-9R was constitutively expressed and exerted a tumor-promoting effect in HCC, whose expression level may be a useful biomarker of tumor invasiveness and patient clinical outcome.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Niu ZS, Niu XJ and Wang M: Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival. World J Hepatol. 7:7–27. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Hanash SM, Baik CS and Kallioniemi O: Emerging molecular biomarkers - blood-based strategies to detect and monitor cancer. Nat Rev Clin Oncol. 8:142–150. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Stassen M, Schmitt E and Bopp T: From interleukin-9 to T helper 9 cells. Ann N Y Acad Sci. 1247:56–68. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Renauld JC, Druez C, Kermouni A, Houssiau F, Uyttenhove C, Van Roost E and Van Snick J: Expression cloning of the murine and human interleukin 9 receptor cDNAs. Proc Natl Acad Sci USA. 89:5690–5694. 1992. View Article : Google Scholar : PubMed/NCBI

7 

Noelle RJ and Nowak EC: Cellular sources and immune functions of interleukin-9. Nat Rev Immunol. 10:683–687. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Goswami R and Kaplan MH: A brief history of IL-9. J Immunol. 186:3283–3288. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Demoulin JB and Renauld JC: Interleukin 9 and its receptor: An overview of structure and function. Int Rev Immunol. 16:345–364. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Druez C, Coulie P, Uyttenhove C and Van Snick J: Functional and biochemical characterization of mouse P40/IL-9 receptors. J Immunol. 145:2494–2499. 1990.PubMed/NCBI

11 

Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J and Renauld JC: A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9. Mol Cell Biol. 16:4710–4716. 1996.PubMed/NCBI

12 

Demoulin JB, Louahed J, Dumoutier L, Stevens M and Renauld JC: MAP kinase activation by interleukin-9 in lymphoid and mast cell lines. Oncogene. 22:1763–1770. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Yamasaki A, Saleh A, Koussih L, Muro S, Halayko AJ and Gounni AS: IL-9 induces CCL11 expression via STAT3 signalling in human airway smooth muscle cells. PLoS One. 5:e91782010. View Article : Google Scholar : PubMed/NCBI

14 

Jäger A, Dardalhon V, Sobel RA, Bettelli E and Kuchroo VK: Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol. 183:7169–7177. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Forbes EE, Groschwitz K, Abonia JP, Brandt EB, Cohen E, Blanchard C, Ahrens R, Seidu L, McKenzie A, Strait R, et al: IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med. 205:897–913. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Sismanopoulos N, Delivanis DA, Alysandratos KD, Angelidou A, Vasiadi M, Therianou A and Theoharides TC: IL-9 induces VEGF secretion from human mast cells and IL-9/IL-9 receptor genes are overexpressed in atopic dermatitis. PLoS One. 7:e332712012. View Article : Google Scholar : PubMed/NCBI

17 

Kearley J, Erjefalt JS, Andersson C, Benjamin E, Jones CP, Robichaud A, Pegorier S, Brewah Y, Burwell TJ, Bjermer L, et al: IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways. Am J Respir Crit Care Med. 183:865–875. 2011. View Article : Google Scholar

18 

Chen N, Lu K, Li P, Lv X and Wang X: Overexpression of IL-9 induced by STAT6 activation promotes the pathogenesis of chronic lymphocytic leukemia. Int J Clin Exp Pathol. 7:2319–2323. 2014.PubMed/NCBI

19 

Shang Y, Kakinuma S, Nishimura M, Kobayashi Y, Nagata K and Shimada Y: Interleukin-9 receptor gene is transcriptionally regulated by nucleolin in T-cell lymphoma cells. Mol Carcinog. 51:619–627. 2012. View Article : Google Scholar

20 

El-Serag HB: Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 142:1264–1273.e1. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Shi JY, Gao Q, Wang ZC, Zhou J, Wang XY, Min ZH, Shi YH, Shi GM, Ding ZB, Ke AW, et al: Margin-infiltrating CD20(+) B cells display an atypical memory phenotype and correlate with favorable prognosis in hepatocellular carcinoma. Clin Cancer Res. 19:5994–6005. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Vitale A, Morales RR, Zanus G, Farinati F, Burra P, Angeli P, Frigo AC, Del Poggio P, Rapaccini G, Di Nolfo MA, et al: Italian Liver Cancer group: Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: A multicentre, cohort study. Lancet Oncol. 12:654–662. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Gao Q, Zhao YJ, Wang XY, Qiu SJ, Shi YH, Sun J, Yi Y, Shi JY, Shi GM, Ding ZB, et al: CXCR6 upregulation contributes to a proinflammatory tumor microenvironment that drives metastasis and poor patient outcomes in hepatocellular carcinoma. Cancer Res. 72:3546–3556. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Shang Y, Kakinuma S, Amasaki Y, Nishimura M, Kobayashi Y and Shimada Y: Aberrant activation of interleukin-9 receptor and downstream Stat3/5 in primary T-cell lymphomas in vivo in susceptible B6 and resistant C3H mice. In Vivo. 22:713–720. 2008.

25 

Chen N and Wang X: Role of IL-9 and STATs in hematological malignancies (Review). Oncol Lett. 7:602–610. 2014.PubMed/NCBI

26 

Barata JT, Keenan TD, Silva A, Nadler LM, Boussiotis VA and Cardoso AA: Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia. Haematologica. 89:1459–1467. 2004.PubMed/NCBI

27 

Glimelius I, Edström A, Amini RM, Fischer M, Nilsson G, Sundström C, Enblad G and Molin D: IL-9 expression contributes to the cellular composition in Hodgkin lymphoma. Eur J Haematol. 76:278–283. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Gruss HJ, Brach MA, Drexler HG, Bross KJ and Herrmann F: Interleukin 9 is expressed by primary and cultured Hodgkin and Reed-Sternberg cells. Cancer Res. 52:1026–1031. 1992.PubMed/NCBI

29 

Nagato T, Kobayashi H, Kishibe K, Takahara M, Ogino T, Ishii H, Oikawa K, Aoki N, Sato K, Kimura S, et al: Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients. Clin Cancer Res. 11:8250–8257. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Wagner EF and Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9:537–549. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li H, Sun Q, Liu L, Zhang J, Huang J, Wang C, Ding R, Song K and Tong Z: High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome. Oncol Rep 34: 795-802, 2015.
APA
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C. ... Tong, Z. (2015). High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome. Oncology Reports, 34, 795-802. https://doi.org/10.3892/or.2015.4060
MLA
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C., Ding, R., Song, K., Tong, Z."High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome". Oncology Reports 34.2 (2015): 795-802.
Chicago
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C., Ding, R., Song, K., Tong, Z."High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome". Oncology Reports 34, no. 2 (2015): 795-802. https://doi.org/10.3892/or.2015.4060
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Sun Q, Liu L, Zhang J, Huang J, Wang C, Ding R, Song K and Tong Z: High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome. Oncol Rep 34: 795-802, 2015.
APA
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C. ... Tong, Z. (2015). High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome. Oncology Reports, 34, 795-802. https://doi.org/10.3892/or.2015.4060
MLA
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C., Ding, R., Song, K., Tong, Z."High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome". Oncology Reports 34.2 (2015): 795-802.
Chicago
Li, H., Sun, Q., Liu, L., Zhang, J., Huang, J., Wang, C., Ding, R., Song, K., Tong, Z."High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome". Oncology Reports 34, no. 2 (2015): 795-802. https://doi.org/10.3892/or.2015.4060
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