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Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy

Overview of attention for article published in Breast Cancer Research, April 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (92nd percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

Mentioned by

news
2 news outlets
twitter
6 tweeters
facebook
1 Facebook page
wikipedia
2 Wikipedia pages

Readers on

mendeley
21 Mendeley
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Title
Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy
Published in
Breast Cancer Research, April 2015
DOI 10.1186/s13058-015-0562-7
Pubmed ID
Authors

Kimberly A Snyder, Michael R Hughes, Bradley Hedberg, Jill Brandon, Diana C Hernaez, Peter Bergqvist, Frederic Cruz, Kelvin Po, Marcia L Graves, Michelle E Turvey, Julie S Nielsen, John A Wilkins, Shaun R McColl, John S Babcook, Calvin D Roskelley, Kelly M McNagny, Diana Canals Hernaez

Abstract

Podocalyxin (gene name PODXL) is a CD34-related sialomucin implicated in the regulation of cell adhesion, migration and polarity. Upregulated expression of podocalyxin is linked to poor patient survival in epithelial cancers. However, it is not known if podocalyxin has a functional role in tumor progression. We silenced podocalyxin expression in the aggressive basal-like human (MDA-MB-231) and mouse (4T1) breast cancer cell-lines and also overexpressed podocalyxin in the more benign human breast cancer cell line, MCF-7. We evaluated how podocalyxin affects tumorsphere-formation in vitro and compared the ability of podocalxyin-deficient (shPODXL) and -replete cell lines to form tumors and metastasize using xenogenic- or syngeneic-transplant models in mice. Finally, in an effort to develop therapeutic treatments for systemic cancers, we generated a series of anti-human podocalyxin antibodies and screened these for their ability to inhibit tumor progression in xenografted mice. Although deletion of podocalyxin does not alter gross cell morphology and growth under standard (adherent) culture conditions, expression of PODXL is required for efficient formation of tumorspheres in vitro. Correspondingly, silencing podocalyxin resulted in attenuated primary tumor growth and invasiveness in mice and severely impaired the formation of distant metastases. Likewise, in competitive tumor engraftment assays where we injected a 50:50 mixture of control and shPODXL (short-hairpin RNA targeting PODXL) cells, we found that podocalyxin-deficient cells exhibit a striking decrease in the ability to form clonal tumors in the lung, liver, and bone marrow. Finally, to validate podocalyxin as a viable target for immunotherapy we screened a series of novel anti-human podocalyxin antibodies for their ability to inhibit tumor progression in vivo. One of these antibodies, PODOC1, potently blocked tumor growth and metastasis. We show that podocalyxin plays a key role in the formation of primary tumors and distant tumor metastasis. In addition, we validate podocalyxin as potential target for monoclonal antibody therapy to inhibit primary tumor growth and systemic dissemination.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 5%
Unknown 20 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 33%
Student > Ph. D. Student 5 24%
Student > Bachelor 3 14%
Student > Postgraduate 2 10%
Student > Doctoral Student 2 10%
Other 2 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 48%
Biochemistry, Genetics and Molecular Biology 3 14%
Medicine and Dentistry 3 14%
Nursing and Health Professions 2 10%
Immunology and Microbiology 1 5%
Other 2 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 23. 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 03 May 2017.
All research outputs
#371,536
of 8,150,286 outputs
Outputs from Breast Cancer Research
#52
of 1,025 outputs
Outputs of similar age
#14,222
of 201,461 outputs
Outputs of similar age from Breast Cancer Research
#5
of 42 outputs
Altmetric has tracked 8,150,286 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,025 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has done particularly well, scoring higher than 94% 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 201,461 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 42 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.