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

  • Published online on: April 7, 2015     https://doi.org/10.3892/or.2015.3903
  • Pages: 2981-2991
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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.
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June-2015
Volume 33 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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