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Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, April 2017
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Title
Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells
Published in
Journal of Experimental & Clinical Cancer Research, April 2017
DOI 10.1186/s13046-017-0528-y
Pubmed ID
Authors

Peiming Zheng, Lei Chen, Xiangliang Yuan, Qin Luo, Yi Liu, Guohua Xie, Yanhui Ma, Lisong Shen

Abstract

Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). However, the resistance often occurs with the mechanisms being not well understood. Recently, emerging evidence indicates that tumor-associated macrophages (TAMs) play an important role in chemoresistance of cancer. As the important mediators in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins to be involved in tumor aggressiveness. The aim of the study was to investigate whether exosomes derived from TAMs mediate cisplatin resistance in gastric cancer. M2 polarized macrophages were obtained from mouse bone marrow or human PBMCs stimulated with IL-4 and IL-13. Exosomes isolated from M2 macrophages culture medium were characterized, and miRNA expression profiles of M2 derived exosomes (M2-exos) were analyzed using miRNA microarray. In vitro cell coculture was further conducted to investigate M2-exos mediated crosstalk between TAMs and tumor cells. Moreover, the in vivo experiments were performed using a subcutaneous transplantation tumor model in athymic nude mice. In this study, we showed that M2 polarized macrophages promoted cisplatin (DDP) resistance in gastric cancer cells and exosomes derived from M2 macrophages (M2-exos) are involved in mediating the resistance to DDP. Using miRNA profiles assay, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and cell lysate isolated from M2 polarized macrophage. Functional studies revealed that exosomal miR-21 can be directly transferred from macrophages to the gastric cancer cells, where it suppresses cell apoptosis and enhances activation of PI3K/AKT signaling pathway by down-regulation of PTEN. Our findings suggest that exosomal transfer of tumor-associated macrophages derived miR-21 confer DDP resistance in gastric cancer, and targeting exosome communication may be a promising new therapeutic strategy for gastric cancer patients.

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The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 183 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 183 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 31 17%
Student > Master 28 15%
Student > Bachelor 17 9%
Researcher 15 8%
Student > Doctoral Student 13 7%
Other 21 11%
Unknown 58 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 51 28%
Medicine and Dentistry 21 11%
Agricultural and Biological Sciences 14 8%
Immunology and Microbiology 7 4%
Pharmacology, Toxicology and Pharmaceutical Science 6 3%
Other 16 9%
Unknown 68 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 30 September 2017.
All research outputs
#14,386,730
of 25,390,692 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#753
of 2,372 outputs
Outputs of similar age
#142,608
of 297,662 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#8
of 23 outputs
Altmetric has tracked 25,390,692 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,372 research outputs from this source. They receive a mean Attention Score of 4.8. This one has gotten more attention than average, scoring higher than 67% 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 297,662 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 23 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 65% of its contemporaries.