Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression
Authors: Weiqi Dang
Tingmei Chen
Xiaofei Wang
Hong Cao
Hao Tang
Xiaozhong Cai
Wenxia Tian
Xiwen Zhang
Lin Wang
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Tumor-associated macrophages; TAMs; M2 polarization; STAT3 signaling; liposomal nanoparticles
Affiliations: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.

Abstract:  Tumor-associated macrophages (TAMs) are essential cellular components within tumor microenvironment (TME). TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10(high), IL-12(low), TGF-β(high). STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs) encapsulating HC were employed to suppress STAT3 activity and "re-educate" TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10(low), IL-12(high), TGF-β(low), and the "re-educated" macrophages (M1-like macrophages) considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression. 

Retracted: No

PubPeer comments:
 2019 Expression of Concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0220672 After publication of this article [1], concerns were raised about Figs 1 and 3: In Fig 1B, lanes 1u20132 of the RAW264.7 u03b2-actin panel appear similar to lanes 1u20132 of the 4T1 u03b2-actin panel. Lanes 1, 2 of the 4T1 STAT3 panel in Fig 1B appear similar to lanes 1, 2 of the STAT3 panel in Fig 3F, although the lanes in the two figures represent different experimental conditions. The authors confirmed that the same u03b2-actin data were knowingly reported in the two panels of Fig 1B and were not considered essential in supporting the experimentu2019s results. The authors also claimed that the STAT3 duplication resulted from a sample labeling error. The authors provided replication data for the u03b2-actin and STAT3 panels of Figs 1B and 3F, but did not provide p-STAT3 data from the same replication experiments. The journal received no further clarification around the replication experiments or the underlying data for other results in this article. As such, the data provided do not fully clarify the issues pertaining to the overall results. In light of the unresolved questions around the control data for experiments reported in Figs 1B and 3F and the availability of the data for the results reported in this article, the PLOS ONE Editors issue this Expression of Concern. Reference 1. Zhang X, Tian W, Cai X, Wang X, Dang W, Tang H, et al. (2013) Hydrazinocurcumin Encapsuled Nanoparticles u201cRe-Educateu201d Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression. PLoS ONE 8(6): e65896. https: doi.org 10.1371 journal.pone.0065896 pmid:23825527 , 
 Here is an illustration of the two sets of panels that look similar over Figures 1B and 3F. These concerns were shared with the journal in July 2014, while the expression of concern was posted in July 2019. ![file] ,