| Title |
T lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate-Binding Protein 1 expression
|
|---|---|
| Published in |
Acta Neuropathologica, January 2018
|
| DOI | 10.1007/s00401-018-1806-2 |
| Pubmed ID | |
| Authors |
Dana A. M. Mustafa, Rute M. S. M. Pedrosa, Marcel Smid, Marcel van der Weiden, Vanja de Weerd, Alex L. Nigg, Cor Berrevoets, Lona Zeneyedpour, Neibla Priego, Manuel Valiente, Theo M. Luider, Reno Debets, John W. M. Martens, John A. Foekens, Anieta M. Sieuwerts, Johan M. Kros |
| Abstract |
The discovery of genes and molecular pathways involved in the formation of brain metastasis would direct the development of therapeutic strategies to prevent this deadly complication of cancer. By comparing gene expression profiles of Estrogen Receptor negative (ER-) primary breast tumors between patients who developed metastasis to brain and to organs other than brain, we found that T lymphocytes promote the formation of brain metastases. To functionally test the ability of T cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB) model. By co-culturing T lymphocytes with breast cancer cells, we confirmed that T cells increase the ability of breast cancer cells to cross the BBB. Proteomics analysis of the tumor cells revealed Guanylate-Binding Protein 1 (GBP1) as a key T lymphocyte-induced protein that enables breast cancer cells to cross the BBB. The GBP1 gene appeared to be up-regulated in breast cancer of patients who developed brain metastasis. Silencing of GBP1 reduced the ability of breast cancer cells to cross the in vitro BBB model. In addition, the findings were confirmed in vivo in an immunocompetent syngeneic mouse model. Co-culturing of ErbB2 tumor cells with activated T cells induced a significant increase in Gbp1 expression by the cancer cells. Intracardial inoculation of the co-cultured tumor cells resulted in preferential seeding to brain. Moreover, intracerebral outgrowth of the tumor cells was demonstrated. The findings point to a role of T cells in the formation of brain metastases in ER- breast cancers, and provide potential targets for intervention to prevent the development of cerebral metastases. |
X Demographics
The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 4 | 36% |
| United States | 2 | 18% |
| United Kingdom | 1 | 9% |
| Unknown | 4 | 36% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 82% |
| Scientists | 2 | 18% |
Mendeley readers
The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 62 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 15% |
| Researcher | 8 | 13% |
| Student > Ph. D. Student | 7 | 11% |
| Student > Master | 5 | 8% |
| Student > Doctoral Student | 4 | 6% |
| Other | 13 | 21% |
| Unknown | 16 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 26% |
| Medicine and Dentistry | 9 | 15% |
| Agricultural and Biological Sciences | 5 | 8% |
| Neuroscience | 4 | 6% |
| Chemistry | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 19 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 09 January 2020.
All research outputs
#3,378,938
of 23,923,788 outputs
Outputs from Acta Neuropathologica
#868
of 2,421 outputs
Outputs of similar age
#76,847
of 446,756 outputs
Outputs of similar age from Acta Neuropathologica
#20
of 36 outputs
Altmetric has tracked 23,923,788 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,421 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.2. This one has gotten more attention than average, scoring higher than 64% 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 446,756 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.