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
June-2015 Volume 33 Issue 6

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
June-2015 Volume 33 Issue 6

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

Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment

  • Authors:
    • Zi Wang
    • Zhixi Li
    • Yuyi Wang
    • Dan Cao
    • Xia Wang
    • Ming Jiang
    • Mei Li
    • Xi Yan
    • Yan Li
    • Yanyang Liu
    • Feng Luo
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 61004, P.R. China
  • Pages: 2981-2991
    |
    Published online on: April 7, 2015
       https://doi.org/10.3892/or.2015.3903
  • 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 systematic application of antiangiogenic therapy remains an issue of concern, mainly due to the hypoxic and inflammatory changes in the tumor microenvironment elicited by antiangiogenic therapy. Versican, a ‘bridge’ connecting inflammation with tumor progression as well as playing a central role in the generation of an inflammatory tumor microenvironment is a promising candidate for the intervention of inflammatory changes in the tumor microenvironment elicited by antiangiogenic therapy. To examine this hypothesis, a short‑hairpin RNA targeting versican (shVCAN) was designed and shVCAN stable‑transfected B16F1 and Lewis lung carcinoma (LLC) cell lines were established. Simultaneously, the established B16F1 and LLC tumor models were used to investigate the effect of versican silencing on the tumor burden of mice. The results showed that, versican silencing exerted an inhibitory effect on the proliferative and migratory ability of B16F1 cells, but did not affect LLC cells. Endostatin exhibited modest inhibition of tumor growth in tumor-bearing mice. Versican silencing alone effectively suppressed orthotopic tumor growth and significantly prolonged survival time of mice more effectively when combined with endostatin. Endostatin elicited inflammatory and immunosuppressive changes in the tumor microenvironment, including an accumulation of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and inflammatory cytokines. In addition, NF-κB and HIF-1α were overexpressed in the tumor. Versican silencing improved the antitumor efficacy of endostatin by alleviating its induced changes in the tumor microenvironment. Thus, versican silencing in the tumor microenvironment offers a promising approach to reverse the tumor refractoriness to antiangiogenic therapies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

View References

1 

Verheul HM, Hammers H, van Erp K, Wei Y, Sanni T, Salumbides B, Qian DZ, Yancopoulos GD and Pili R: Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model. Clin Cancer Res. 13:4201–4208. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D and Casanovas O: Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 15:220–231. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Ellika S, Schultz L and Mikkelsen T: Efficacy, safety and patterns of response and recurrence in patients with recurrent highgrade gliomas treated with bevacizumab plus irinotecan. J Neurooncol. 91:329–336. 2009. View Article : Google Scholar

4 

Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP and Ferrara N: Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol. 25:911–920. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Soeda S, Nakamura N, Ozeki T, Nishiyama H, Hojo H, Yamada H, Abe M and Sato A: Tumor-associated macrophages correlate with vascular space invasion and myometrial invasion in endometrial carcinoma. Gynecol Oncol. 109:122–128. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Kischel P, Waltregny D, Dumont B, Turtoi A, Greffe Y, Kirsch S, De Pauw E and Castronovo V: Versican overexpression in human breast cancer lesions: Known and new isoforms for stromal tumor targeting. Int J Cancer. 126:640–650. 2010. View Article : Google Scholar

7 

Wang W, Xu GL, Jia WD, Ma JL, Li JS, Ge YS, Ren WH, Yu JH and Liu WB: Ligation of TLR2 by versican: A link between inflammation and metastasis. Arch Med Res. 40:321–323. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL and Karin M: Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 457:102–106. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Gao D, Joshi N, Choi H, Ryu S, Hahn M, Catena R, Sadik H, Argani P, Wagner P, Vahdat LT, et al: Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res. 72:1384–1394. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Ling Y, Yang Y, Lu N, You QD, Wang S, Gao Y, Chen Y and Guo QL: Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. Biochem Biophys Res Commun. 361:79–84. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Wang HL, Ning T, Li M, Lu ZJ, Yan X, Peng Q, Lei N, Zhang H and Luo F: Effect of endostatin on preventing postoperative progression of distant metastasis in a murine lung cancer model. Tumori. 97:787–793. 2011.

12 

Ning T, Yan X, Lu ZJ, Wang GP, Zhang NG, Yang JL, Jiang SS, Wu Y, Yang L, Guan YS, et al: Gene therapy with the angiogenesis inhibitor endostatin in an orthotopic lung cancer murine model. Hum Gene Ther. 20:103–111. 2009. View Article : Google Scholar

13 

Ning T, Jiang M, Peng Q, Xi Y, Lu ZJ, Peng YL, Wang HL, Lei N, Zhang H, Lin HJ, et al: Low-dose endostatin normalizes the structure and function of tumor vasculature and improves the delivery and anti-tumor efficacy of cytotoxic drugs in a lung cancer xenograft murine model. Thorac Cancer. 3:229–238. 2012. View Article : Google Scholar

14 

Huang G and Chen L: Discrepancies between antiangiogenic and antitumor effects of recombinant human endostatin. Cancer Biother Radiopharm. 24:589–596. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Zhang H, Wang Z, Peng Q, Liu YY, Zhang W, Wu L, Wang X and Luo F: Tumor refractoriness to endostatin anti-angiogenesis is associated with the recruitment of CD11b+Gr1+ myeloid cells and inflammatory cytokines. Tumori. 99:723–733. 2013.

16 

Li XQ, Shang BY, Wang DC, Zhang SH, Wu SY and Zhen YS: Endostar, a modified recombinant human endostatin, exhibits synergistic effects with dexamethasone on angiogenesis and hepatoma growth. Cancer Lett. 301:212–220. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Ben-Neriah Y and Karin M: Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 12:715–723. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Hernández D, Miquel-Serra L, Docampo MJ, Marco-Ramell A and Bassols A: Role of versican V0/V1 and CD44 in the regulation of human melanoma cell behavior. Int J Mol Med. 27:269–275. 2011.

19 

Zheng PS, Wen J, Ang LC, Sheng W, Viloria-Petit A, Wang Y, Wu Y, Kerbel RS and Yang BB: Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB J. 18:754–756. 2004.PubMed/NCBI

20 

Ostrand-Rosenberg S and Sinha P: Myeloid-derived suppressor cells: Linking inflammation and cancer. J Immunol. 182:4499–4506. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Gabrilovich DI and Nagaraj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 9:162–174. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Shojaei F, Wu X, Qu X, Kowanetz M, Yu L, Tan M, Meng YG and Ferrara N: G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci USA. 106:6742–6747. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Carbone C, Moccia T, Zhu C, Paradiso G, Budillon A, Chiao PJ, Abbruzzese JL and Melisi D: Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype. Clin Cancer Res. 17:5822–5832. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Gordon S and Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol. 5:953–964. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Pollard JW: Trophic macrophages in development and disease. Nat Rev Immunol. 9:259–270. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Sica A and Bronte V: Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest. 117:1155–1166. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Martinez FO, Helming L and Gordon S: Alternative activation of macrophages: An immunologic functional perspective. Annu Rev Immunol. 27:451–483. 2009. View Article : Google Scholar

28 

Mantovani A, Bottazzi B, Colotta F, Sozzani S and Ruco L: The origin and function of tumor-associated macrophages. Immunol Today. 13:265–270. 1992. View Article : Google Scholar : PubMed/NCBI

29 

Mantovani A and Sica A: Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Curr Opin Immunol. 22:231–237. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Qian BZ and Pollard JW: Macrophage diversity enhances tumor progression and metastasis. Cell. 141:39–51. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Sica A, Saccani A and Mantovani A: Tumor-associated macrophages: A molecular perspective. Int Immunopharmacol. 2:1045–1054. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Kim YJ, Jung EB, Lee MS, Seo SJ, Kim MH, Lee MW and Lee CS: Rotundarpene inhibits toll-like receptor 2 activation-induced production of inflammatory mediators in keratinocytes by suppressing the Akt and NF-κB pathways. Int Immunopharmacol. 18:325–332. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang Z, Li Z, Wang Y, Cao D, Wang X, Jiang M, Li M, Yan X, Li Y, Liu Y, Liu Y, et al: Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment. Oncol Rep 33: 2981-2991, 2015.
APA
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M. ... Luo, F. (2015). Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment. Oncology Reports, 33, 2981-2991. https://doi.org/10.3892/or.2015.3903
MLA
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M., Li, M., Yan, X., Li, Y., Liu, Y., Luo, F."Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment". Oncology Reports 33.6 (2015): 2981-2991.
Chicago
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M., Li, M., Yan, X., Li, Y., Liu, Y., Luo, F."Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment". Oncology Reports 33, no. 6 (2015): 2981-2991. https://doi.org/10.3892/or.2015.3903
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z, Li Z, Wang Y, Cao D, Wang X, Jiang M, Li M, Yan X, Li Y, Liu Y, Liu Y, et al: Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment. Oncol Rep 33: 2981-2991, 2015.
APA
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M. ... Luo, F. (2015). Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment. Oncology Reports, 33, 2981-2991. https://doi.org/10.3892/or.2015.3903
MLA
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M., Li, M., Yan, X., Li, Y., Liu, Y., Luo, F."Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment". Oncology Reports 33.6 (2015): 2981-2991.
Chicago
Wang, Z., Li, Z., Wang, Y., Cao, D., Wang, X., Jiang, M., Li, M., Yan, X., Li, Y., Liu, Y., Luo, F."Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment". Oncology Reports 33, no. 6 (2015): 2981-2991. https://doi.org/10.3892/or.2015.3903
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