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

Wang X, Zhao F, He X, Wang J, Zhang Y, Zhang H, Ni Y, Sun J, Wang X, Dou J - Oncotarget (2015)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus

Histological analysis of lungs and lymph nodes of melanoma bearing miceA. Tissue sections derived from melanoma bearing mice 51 days after vaccination followed by challenge with the differently treated cells. The top and bottom panels show the lung sections and the lymph node sections, respectively. The arrows point to the metastatic focus as described in the text. B and C. Quantitative analysis of the tumor metastatic rates of lungs and lymph nodes, respectively, in the differently treated mice; refer to the statistical differences as indicated.
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Figure 6: Histological analysis of lungs and lymph nodes of melanoma bearing miceA. Tissue sections derived from melanoma bearing mice 51 days after vaccination followed by challenge with the differently treated cells. The top and bottom panels show the lung sections and the lymph node sections, respectively. The arrows point to the metastatic focus as described in the text. B and C. Quantitative analysis of the tumor metastatic rates of lungs and lymph nodes, respectively, in the differently treated mice; refer to the statistical differences as indicated.

Mentions: The results from the tumorigenicity and the tumor lung metastasis counts suggested that the synergism antitumor efficacy was found in the mice immunized with the tumor vaccine B16F10/GPI-IL-21 and then challenged by the B16F10-shTGF-β1 cells and the injection of miR200c agomir (Figure 5). Also, these findings were supported by the histological pathologic analysis of the different sections derived from the mice. Figure 6A portrays the apparent metastatic focus seen in the lungs and lymph nodes of the mice challenged by B16F10/shTGF-β1 or challenged by B16F10/shTGF-β1 with the injection of miR200c agomir, even in the B16F10/GPI-IL-21 vaccinated mice with the B16F10/shTGF-β1 challenge. We also found no tumor metastatic focus in the livers, kidneys, and hearts of the experiment mice until 51 days into the observation (data not shown here).


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

Wang X, Zhao F, He X, Wang J, Zhang Y, Zhang H, Ni Y, Sun J, Wang X, Dou J - Oncotarget (2015)

Histological analysis of lungs and lymph nodes of melanoma bearing miceA. Tissue sections derived from melanoma bearing mice 51 days after vaccination followed by challenge with the differently treated cells. The top and bottom panels show the lung sections and the lymph node sections, respectively. The arrows point to the metastatic focus as described in the text. B and C. Quantitative analysis of the tumor metastatic rates of lungs and lymph nodes, respectively, in the differently treated mice; refer to the statistical differences as indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494953&req=5

Figure 6: Histological analysis of lungs and lymph nodes of melanoma bearing miceA. Tissue sections derived from melanoma bearing mice 51 days after vaccination followed by challenge with the differently treated cells. The top and bottom panels show the lung sections and the lymph node sections, respectively. The arrows point to the metastatic focus as described in the text. B and C. Quantitative analysis of the tumor metastatic rates of lungs and lymph nodes, respectively, in the differently treated mice; refer to the statistical differences as indicated.
Mentions: The results from the tumorigenicity and the tumor lung metastasis counts suggested that the synergism antitumor efficacy was found in the mice immunized with the tumor vaccine B16F10/GPI-IL-21 and then challenged by the B16F10-shTGF-β1 cells and the injection of miR200c agomir (Figure 5). Also, these findings were supported by the histological pathologic analysis of the different sections derived from the mice. Figure 6A portrays the apparent metastatic focus seen in the lungs and lymph nodes of the mice challenged by B16F10/shTGF-β1 or challenged by B16F10/shTGF-β1 with the injection of miR200c agomir, even in the B16F10/GPI-IL-21 vaccinated mice with the B16F10/shTGF-β1 challenge. We also found no tumor metastatic focus in the livers, kidneys, and hearts of the experiment mice until 51 days into the observation (data not shown here).

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus