| Title |
Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion
|
|---|---|
| Published in |
Angiogenesis, December 2011
|
| DOI | 10.1007/s10456-011-9241-1 |
| Pubmed ID | |
| Authors |
Marco Mineo, Susan H. Garfield, Simona Taverna, Anna Flugy, Giacomo De Leo, Riccardo Alessandro, Elise C. Kohn |
| Abstract |
Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell communication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were internalized by HUVECs during tubular differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection. Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiotube formation over a serum/growth factor-limited medium control, doubling total cumulative tube length (P = 0.003). Treatment of K562 cells with two clinically active tyrosine kinase inhibitors, imatinib and dasatinib, reduced their total exosome release (P < 0.009); equivalent concentrations of drug-treated exosomes induced a similar extent of tubular differentiation. However, dasatinib treatment of HUVECs markedly inhibited HUVEC response to drug control CML exosomes (P < 0.002). In an in vivo mouse Matrigel plug model angiogenesis was induced by K562 exosomes and abrogated by oral dasatinib treatment (P < 0.01). K562 exosomes induced dasatinib-sensitive Src phosphorylation and activation of downstream Src pathway proteins in HUVECs. Imatinib was minimally active against exosome stimulation of HUVEC cell differentiation and signaling. Thus, CML cell-derived exosomes induce angiogenic activity in HUVEC cells. The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 203 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | <1% |
| Spain | 2 | <1% |
| France | 1 | <1% |
| Uruguay | 1 | <1% |
| Belgium | 1 | <1% |
| Netherlands | 1 | <1% |
| Brazil | 1 | <1% |
| Denmark | 1 | <1% |
| Unknown | 193 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 44 | 22% |
| Researcher | 39 | 19% |
| Student > Doctoral Student | 20 | 10% |
| Student > Bachelor | 19 | 9% |
| Student > Master | 14 | 7% |
| Other | 31 | 15% |
| Unknown | 36 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 59 | 29% |
| Biochemistry, Genetics and Molecular Biology | 44 | 22% |
| Medicine and Dentistry | 35 | 17% |
| Immunology and Microbiology | 8 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 2% |
| Other | 8 | 4% |
| Unknown | 44 | 22% |
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 08 November 2013.
All research outputs
#14,164,797
of 22,701,287 outputs
Outputs from Angiogenesis
#315
of 536 outputs
Outputs of similar age
#153,196
of 243,234 outputs
Outputs of similar age from Angiogenesis
#6
of 9 outputs
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So far Altmetric has tracked 536 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
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