| Title |
Antiangiogenic therapy promoted metastasis of hepatocellular carcinoma by suppressing host-derived interleukin-12b in mouse models
|
|---|---|
| Published in |
Angiogenesis, May 2013
|
| DOI | 10.1007/s10456-013-9357-6 |
| Pubmed ID | |
| Authors |
Xiao-Dong Zhu, Hui-Chuan Sun, Hua-Xiang Xu, Ling-Qun Kong, Zong-Tao Chai, Lu Lu, Ju-Bo Zhang, Dong-Mei Gao, Wen-Quan Wang, Wei Zhang, Peng-Yuan Zhuang, Wei-Zhong Wu, Lu Wang, Zhao-You Tang |
| Abstract |
Antiangiogenic therapy, specially sorafenib, has become the standard of care for patients with advanced hepatocellular carcinoma (HCC), however, the improvement in survival time is not satisfactory. Previous studies have found that, in some circumstances, antiangiogenic therapy promoted tumor metastasis and the mechanistic studies were mainly focus on cancer-cell-autonomous manners. In two experimental metastasis models with tail-vein injection with hepatoma cells and an orthotopic HCC mouse model, we found that pretreatment with two vascular endothelial growth factor receptor (VEGFR) inhibitors, sunitinib and sorafenib, facilitated tumor cell survival in blood stream and promoted lung metastasis from tumors that were subsequently incubated after drug discontinuation, indicating that host response joined into the pro-metastatic effects. An antibody microarray identified that interleukin (IL)-12b was decreased in the peripheral blood of the mice treated with the two VEGFR inhibitors. IL-12b suppression in macrophages and dendritic cells from host organs was found to play a crucial role in treatment-induced metastasis. Supplement with recombinant mouse IL-12b or restoration of IL-12b expression in the host by zoledronic acid, which was previously reported to enhance IL-12 expression in vitro and in vivo, alleviated the metastasis-promoting effects of sunitinib and sorafenib. These studies suggest that host response to VEGFR inhibitors facilitates HCC metastasis and restoration of IL-12b expression could translate into clinical benefits. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 5% |
| Unknown | 21 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 27% |
| Student > Master | 3 | 14% |
| Other | 2 | 9% |
| Student > Bachelor | 2 | 9% |
| Student > Ph. D. Student | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 5 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 41% |
| Agricultural and Biological Sciences | 4 | 18% |
| Biochemistry, Genetics and Molecular Biology | 2 | 9% |
| Social Sciences | 1 | 5% |
| Unknown | 6 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 May 2014.
All research outputs
#17,689,573
of 22,711,645 outputs
Outputs from Angiogenesis
#381
of 536 outputs
Outputs of similar age
#139,552
of 195,172 outputs
Outputs of similar age from Angiogenesis
#7
of 8 outputs
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