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The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009

VNP20009 is a very effective anti-cancer agent and can specifically target tumors and inhibit tumor growth. It was assumed that the tumor targeting ability of VNP20009 correlated to its anticancer capacity. However, our observation contradicted to this assumption. Three VNP20009 mutant strains (Δsly...

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Autores principales: Zhang, Xiaoxin, Xu, Qiaoqiao, Yang, Lirun, Lai, Yueyang, Zhang, Zhuangzhuang, Han, Chao, Jiang, Chizhou, Li, Jiahuang, Shi, Yixin, Hua, Zi-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348385/
https://www.ncbi.nlm.nih.gov/pubmed/27835896
http://dx.doi.org/10.18632/oncotarget.13217
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author Zhang, Xiaoxin
Xu, Qiaoqiao
Yang, Lirun
Lai, Yueyang
Zhang, Zhuangzhuang
Han, Chao
Jiang, Chizhou
Li, Jiahuang
Shi, Yixin
Hua, Zi-Chun
author_facet Zhang, Xiaoxin
Xu, Qiaoqiao
Yang, Lirun
Lai, Yueyang
Zhang, Zhuangzhuang
Han, Chao
Jiang, Chizhou
Li, Jiahuang
Shi, Yixin
Hua, Zi-Chun
author_sort Zhang, Xiaoxin
collection PubMed
description VNP20009 is a very effective anti-cancer agent and can specifically target tumors and inhibit tumor growth. It was assumed that the tumor targeting ability of VNP20009 correlated to its anticancer capacity. However, our observation contradicted to this assumption. Three VNP20009 mutant strains (ΔslyA, ΔSTM3120 and ΔhtrA) with reduced fitness in normal tissues and unchanged fitness in tumors partially or completely lost their anti-cancer capacities. The genes slyA, STM3120 and htrA were required for survival within macrophages and were indispensable for tumor microenvironment remodeling by VNP20009. The infiltration of immune cells occurred less in the tumors of mice infected with the mutant strains. In addition, the mRNA levels of TNF-α and IL-1β were significantly decreased in the tumors of mice treated with the mutant strains. Our results indicate that the immune responses elicited by bacteria rather than the bacterial titer in tumors play a “decisive” role in VNP20009-mediated bacterial cancer therapy, which provides a novel perspective for the underlying mechanism of bacterial cancer therapy.
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spelling pubmed-53483852017-03-31 The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009 Zhang, Xiaoxin Xu, Qiaoqiao Yang, Lirun Lai, Yueyang Zhang, Zhuangzhuang Han, Chao Jiang, Chizhou Li, Jiahuang Shi, Yixin Hua, Zi-Chun Oncotarget Research Paper VNP20009 is a very effective anti-cancer agent and can specifically target tumors and inhibit tumor growth. It was assumed that the tumor targeting ability of VNP20009 correlated to its anticancer capacity. However, our observation contradicted to this assumption. Three VNP20009 mutant strains (ΔslyA, ΔSTM3120 and ΔhtrA) with reduced fitness in normal tissues and unchanged fitness in tumors partially or completely lost their anti-cancer capacities. The genes slyA, STM3120 and htrA were required for survival within macrophages and were indispensable for tumor microenvironment remodeling by VNP20009. The infiltration of immune cells occurred less in the tumors of mice infected with the mutant strains. In addition, the mRNA levels of TNF-α and IL-1β were significantly decreased in the tumors of mice treated with the mutant strains. Our results indicate that the immune responses elicited by bacteria rather than the bacterial titer in tumors play a “decisive” role in VNP20009-mediated bacterial cancer therapy, which provides a novel perspective for the underlying mechanism of bacterial cancer therapy. Impact Journals LLC 2016-11-08 /pmc/articles/PMC5348385/ /pubmed/27835896 http://dx.doi.org/10.18632/oncotarget.13217 Text en Copyright: © 2016 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Xiaoxin
Xu, Qiaoqiao
Yang, Lirun
Lai, Yueyang
Zhang, Zhuangzhuang
Han, Chao
Jiang, Chizhou
Li, Jiahuang
Shi, Yixin
Hua, Zi-Chun
The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title_full The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title_fullStr The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title_full_unstemmed The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title_short The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009
title_sort genes slya, stm3120 and htra are required for the anticancer ability of vnp20009
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348385/
https://www.ncbi.nlm.nih.gov/pubmed/27835896
http://dx.doi.org/10.18632/oncotarget.13217
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