Combining TGF-β1 knockdown and miR200c administration to optimize antitumor efficacy of B16F10/GPI-IL-21 vaccine.

Abstract

TGF-β1 secreted abundantly by tumors cells as well as present in the local microenvironment promotes neoplasm invasion and metastasis by triggering the epithelial to mesenchymal transition (EMT). MiR200c has been shown to suppress EMT and to regulate the cellular epithelial and interstitial state conversion, whereas the tumor vaccines are intended to specifically initiate or amplify a host response against evolving tumor cells. Our study aimed at optimizing the antitumor effects of the B16F10/glycosylphosphatidylinositol-interleukin 21 (B16F10/GPI-IL-21) tumor vaccine on melanoma bearing mice by combining the TGF-β1 knockdown and the administration of miR200c agomir. The mice were subcutaneously vaccinated with inactivated B16F10/GPI-IL-21 vaccine and challenged by B16F10 cells transfected with shTGF-β1 (B16F10/shTGF-β1 cells) or B16F10/shTGF-β1 cells with the administration of miR200c agomir. The later combination showed that, when compared with the mice in the control group that received no vaccination, vaccinated mice significantly increased NK and CTL activities, enhanced levels of IFN-γ, and reduced expression of TGF-β1, N-cadherin, Vimentin, Gli1/2, P-Smad2/3 and others involved in promoting expression of EMT-related molecules in tumor areas, and inhibited the melanoma metastasis in lungs and lymph nodes. Altogether, our findings demonstrate that this synergistic anti-cancer regimen effectively induces strong immune response and diminishes the melanoma progression.

• Authors: Xiaoying Wang, Fengshu Zhao, Xiangfeng He, Jing Wang, Ying Zhang, Hongyi Zhang, Yaoyao Ni, Jianan Sun, Xiaobing Wang, Jun Dou
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 14 Pg. 12493-504 (May 20 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25895132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• MicroRNAs
• Mirn200 microRNA, mouse
• Transforming Growth Factor beta1

Topics

• Animals
• Blotting, Western
• Cancer Vaccines (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Epithelial-Mesenchymal Transition (immunology)
• Flow Cytometry
• Gene Knockdown Techniques
• Immunohistochemistry
• Melanoma, Experimental (pathology, therapy)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (agonists)
• Transforming Growth Factor beta1 (antagonists & inhibitors)