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Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors

Overview of attention for article published in Cell & Bioscience, December 2015
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Title
Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors
Published in
Cell & Bioscience, December 2015
DOI 10.1186/s13578-015-0064-4
Pubmed ID
Authors

Yuyi Wang, Ming Jiang, Zhixi Li, Jiantao Wang, Chi Du, Liu Yanyang, Yang Yu, Xia Wang, Nan Zhang, Maoyuan Zhao, Li Wang, Mei Li, Feng Luo

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide, and treatments for lung cancer have a high failure rate. Anti-angiogenic therapy is also often ineffective because of refractory disease. Endostatin (ES) is one of the most widely-used anti-angiogenic drugs for lung cancer in China, and resistance to it is a barrier that needs to be resolved. It has been shown that myeloid-derived suppressor cells (MDSCs) are involved in resistance to ES. Whether other cells and/or cell factors in the tumor microenvironment that have been shown to be related to resistance to other anti-cancer drugs are also involved in ES resistance is unknown. In this study, we showed that after continuously treatment with ES for 12 days, volumes of A549 transplantation tumors of mice reached the sizes of tumors which were borne by mice that were treated with normal saline and this meant that resistance to ES appeared. Cancer stem cells (CSCs), which have been widely accepted as one of reasons responsible for resistance to many anti-tumor drugs were also being discovered increased proportionally in A549 transplantation tumors after ES treatment for 12 days. During further exploration of reasons for this increase, we discovered that after ES treatment, microvessel density and vascular endothelial growth factor level was decreased in tumors, whereas transforming growth factor (TGF)-β1 level was elevated, and MDSCs, one of the sources of TGF-β1, were also increased. We speculate that hypoxia and TGF-β1 are responsible for the increased CSC number in A549 transplantation tumors. By using cobalt chloride to mimic hypoxia and human recombinant TGF-β1 in vitro, we found that hypoxia and TGF-β1can indeed enhance the stemness of A549 cells. In addition, the inductive effect of hypoxia is stronger than TGF-β1, and the combination of both is stronger than either alone, which is first report of such a finding, to our knowledge. Increased TGF-β1 and strengthened hypoxia in A549 transplantation tumors, as a result of ES therapy, cooperatively increase proportion of CSCs that are involved in ES resistance which was revealed by failure of tumor volume repression after continuously treatment with ES for 12 days.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 33%
Student > Master 3 25%
Student > Ph. D. Student 1 8%
Student > Postgraduate 1 8%
Researcher 1 8%
Other 2 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 42%
Medicine and Dentistry 3 25%
Agricultural and Biological Sciences 1 8%
Immunology and Microbiology 1 8%
Unspecified 1 8%
Other 1 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 26 December 2015.
All research outputs
#3,164,482
of 6,882,666 outputs
Outputs from Cell & Bioscience
#59
of 164 outputs
Outputs of similar age
#136,894
of 295,873 outputs
Outputs of similar age from Cell & Bioscience
#10
of 31 outputs
Altmetric has tracked 6,882,666 research outputs across all sources so far. This one has received more attention than most of these and is in the 51st percentile.
So far Altmetric has tracked 164 research outputs from this source. They receive a mean Attention Score of 2.1. This one has gotten more attention than average, scoring higher than 58% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 295,873 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.