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Tumour macrophages as potential targets of bisphosphonates

Overview of attention for article published in Journal of Translational Medicine, October 2011
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  • Good Attention Score compared to outputs of the same age (73rd percentile)
  • Good Attention Score compared to outputs of the same age and source (74th percentile)

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2 tweeters
3 patents


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216 Mendeley
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Tumour macrophages as potential targets of bisphosphonates
Published in
Journal of Translational Medicine, October 2011
DOI 10.1186/1479-5876-9-177
Pubmed ID

Thea L Rogers, Ingunn Holen


Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use.Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to bisphosphonates in model studies; In vitro, zoledronic acid causes increased apoptotic cell death; in vivo the drug has been shown to inhibit the production of pro-angiogenic factor MMP-9, as well as most recent evidence showing it can trigger the reversal of the TAMs phenotype from pro-tumoral M2 to tumoricidal M1. There is thus accumulating evidence supporting the hypothesis that effects on TAMs may contribute to the anti-tumour effect of bisphosphonates. This review will focus in detail on the role of tumour associated macrophages in breast cancer progression, the actions of bisphosphonates on macrophages in vitro and in tumour models in vivo and summarise the evidence supporting the potential for the targeting of tumour macrophages with bisphosphonates.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 216 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 1%
United Kingdom 1 <1%
Denmark 1 <1%
Brazil 1 <1%
Unknown 210 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 54 25%
Student > Ph. D. Student 45 21%
Student > Master 31 14%
Student > Bachelor 18 8%
Student > Doctoral Student 11 5%
Other 32 15%
Unknown 25 12%
Readers by discipline Count As %
Medicine and Dentistry 53 25%
Agricultural and Biological Sciences 53 25%
Biochemistry, Genetics and Molecular Biology 23 11%
Chemistry 13 6%
Immunology and Microbiology 13 6%
Other 24 11%
Unknown 37 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 11 July 2019.
All research outputs
of 17,349,416 outputs
Outputs from Journal of Translational Medicine
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Outputs of similar age
of 120,241 outputs
Outputs of similar age from Journal of Translational Medicine
of 50 outputs
Altmetric has tracked 17,349,416 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 3,202 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.9. This one has done well, scoring higher than 78% 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 120,241 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 73% of its contemporaries.
We're also able to compare this research output to 50 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 74% of its contemporaries.