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Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk

Overview of attention for article published in Breast Cancer Research, July 2012
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Title
Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk
Published in
Breast Cancer Research, July 2012
DOI 10.1186/bcr3217
Pubmed ID
Authors

Lauren A Matise, Trenis D Palmer, William J Ashby, Abudi Nashabi, Anna Chytil, Mary Aakre, Michael W Pickup, Agnieszka E Gorska, Andries Zijlstra, Harold L Moses

Abstract

Transforming growth factor beta (TGF-β) has a dual role during tumor progression, initially as a suppressor and then as a promoter. Epithelial TGF-β signaling regulates fibroblast recruitment and activation. Concurrently, TGF-β signaling in stromal fibroblasts suppresses tumorigenesis in adjacent epithelia, while its ablation potentiates tumor formation. Much is known about the contribution of TGF-β signaling to tumorigenesis, yet the role of TGF-β in epithelial-stromal migration during tumor progression is poorly understood. We hypothesize that TGF-β is a critical regulator of tumor-stromal interactions that promote mammary tumor cell migration and invasion. Fluorescently labeled murine mammary carcinoma cells, isolated from either MMTV-PyVmT transforming growth factor-beta receptor II knockout (TβRII KO) or TβRIIfl/fl control mice, were combined with mammary fibroblasts and xenografted onto the chicken embryo chorioallantoic membrane. These combinatorial xenografts were used as a model to study epithelial-stromal crosstalk. Intravital imaging of migration was monitored ex ovo, and metastasis was investigated in ovo. Epithelial RNA from in ovo tumors was isolated by laser capture microdissection and analyzed to identify gene expression changes in response to TGF-β signaling loss. Intravital microscopy of xenografts revealed that mammary fibroblasts promoted two migratory phenotypes dependent on epithelial TGF-β signaling: single cell/strand migration or collective migration. At epithelial-stromal boundaries, single cell/strand migration of TβRIIfl/fl carcinoma cells was characterized by expression of α-smooth muscle actin and vimentin, while collective migration of TβRII KO carcinoma cells was identified by E-cadherin+/p120+/β-catenin+ clusters. TβRII KO tumors also exhibited a twofold greater metastasis than TβRIIfl/fl tumors, attributed to enhanced extravasation ability. In TβRII KO tumor epithelium compared with TβRIIfl/fl epithelium, Igfbp4 and Tspan13 expression was upregulated while Col1α2, Bmp7, Gng11, Vcan, Tmeff1, and Dsc2 expression was downregulated. Immunoblotting and quantitative PCR analyses on cultured cells validated these targets and correlated Tmeff1 expression with disease progression of TGF-β-insensitive mammary cancer. Fibroblast-stimulated carcinoma cells utilize TGF-β signaling to drive single cell/strand migration but migrate collectively in the absence of TGF-β signaling. These migration patterns involve the signaling regulation of several epithelial-to-mesenchymal transition pathways. Our findings concerning TGF-β signaling in epithelial-stromal interactions are important in identifying migratory mechanisms that can be targeted as recourse for breast cancer treatment.

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X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 115 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 4 3%
Netherlands 1 <1%
Portugal 1 <1%
United Kingdom 1 <1%
Sweden 1 <1%
Unknown 107 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 18%
Researcher 17 15%
Student > Master 11 10%
Student > Bachelor 11 10%
Professor 9 8%
Other 21 18%
Unknown 25 22%
Readers by discipline Count As %
Agricultural and Biological Sciences 46 40%
Biochemistry, Genetics and Molecular Biology 16 14%
Medicine and Dentistry 10 9%
Engineering 5 4%
Mathematics 1 <1%
Other 5 4%
Unknown 32 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 04 September 2012.
All research outputs
#20,656,161
of 25,374,647 outputs
Outputs from Breast Cancer Research
#1,706
of 2,053 outputs
Outputs of similar age
#139,012
of 177,582 outputs
Outputs of similar age from Breast Cancer Research
#34
of 42 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,053 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
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 177,582 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.
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 is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.