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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, March 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)

Mentioned by

news
2 news outlets
twitter
4 tweeters
patent
3 patents
facebook
1 Facebook page
wikipedia
3 Wikipedia pages

Citations

dimensions_citation
44 Dimensions

Readers on

mendeley
64 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, March 2015
DOI 10.1186/s13058-015-0562-7
Pubmed ID
Authors

Kimberly A Snyder, Michael R Hughes, Bradley Hedberg, Jill Brandon, Diana Canals 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

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 4 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 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 2 3%
Unknown 62 97%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 14 22%
Researcher 14 22%
Student > Ph. D. Student 11 17%
Student > Doctoral Student 3 5%
Professor > Associate Professor 3 5%
Other 10 16%
Unknown 9 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 23%
Biochemistry, Genetics and Molecular Biology 13 20%
Medicine and Dentistry 12 19%
Neuroscience 3 5%
Immunology and Microbiology 3 5%
Other 6 9%
Unknown 12 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 27. 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 21 June 2020.
All research outputs
#874,078
of 17,356,510 outputs
Outputs from Breast Cancer Research
#82
of 1,704 outputs
Outputs of similar age
#14,857
of 232,224 outputs
Outputs of similar age from Breast Cancer Research
#1
of 1 outputs
Altmetric has tracked 17,356,510 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,704 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one has done particularly well, scoring higher than 95% 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 232,224 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 93% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them