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Inhibition of integrin αVβ6 changes fibril thickness of stromal collagen in experimental carcinomas

Overview of attention for article published in Cell Communication and Signaling, July 2018
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3 tweeters

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7 Mendeley
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Title
Inhibition of integrin αVβ6 changes fibril thickness of stromal collagen in experimental carcinomas
Published in
Cell Communication and Signaling, July 2018
DOI 10.1186/s12964-018-0249-7
Pubmed ID
Authors

P. Olof Olsson, Renata Gustafsson, Alexei V. Salnikov, Maria Göthe, Kathrin S. Zeller, Tomas Friman, Bo Baldetorp, Louise A. Koopman, Paul H. Weinreb, Shelia M. Violette, Sebastian Kalamajski, Nils-Erik Heldin, Kristofer Rubin

Abstract

Chemotherapeutic efficacy can be improved by targeting the structure and function of the extracellular matrix (ECM) in the carcinomal stroma. This can be accomplished by e.g. inhibiting TGF-β1 and -β3 or treating with Imatinib, which results in scarcer collagen fibril structure in xenografted human KAT-4/HT29 (KAT-4) colon adenocarcinoma. The potential role of αVβ6 integrin-mediated activation of latent TGF-β was studied in cultured KAT-4 and Capan-2 human ductal pancreatic carcinoma cells as well as in xenograft carcinoma generated by these cells. The monoclonal αVβ6 integrin-specific monoclonal antibody 3G9 was used to inhibit the αVβ6 integrin activity. Both KAT-4 and Capan-2 cells expressed the αVβ6 integrin but only KAT-4 cells could utilize this integrin to activate latent TGF-β in vitro. Only when Capan-2 cells were co-cultured with human F99 fibroblasts was the integrin activation mechanism triggered, suggesting a more complex, fibroblast-dependent, activation pathway. In nude mice, a 10-day treatment with 3G9 reduced collagen fibril thickness and interstitial fluid pressure in KAT-4 but not in the more desmoplastic Capan-2 tumors that, to achieve a similar effect, required a prolonged 3G9 treatment. In contrast, a 10-day direct inhibition of TGF-β1 and -β3 reduced collagen fibril thickness in both tumor models. Our data demonstrate that the αVβ6-directed activation of latent TGF-β plays a pivotal role in modulating the stromal collagen network in carcinoma, but that the sensitivity to αVβ6 inhibition depends on the simultaneous presence of alternative paths for latent TGF-β activation and the extent of desmoplasia.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 43%
Student > Master 2 29%
Student > Ph. D. Student 1 14%
Unknown 1 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 43%
Arts and Humanities 1 14%
Agricultural and Biological Sciences 1 14%
Immunology and Microbiology 1 14%
Unknown 1 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 July 2018.
All research outputs
#7,635,901
of 13,255,897 outputs
Outputs from Cell Communication and Signaling
#120
of 369 outputs
Outputs of similar age
#137,749
of 267,751 outputs
Outputs of similar age from Cell Communication and Signaling
#3
of 5 outputs
Altmetric has tracked 13,255,897 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 369 research outputs from this source. They receive a mean Attention Score of 2.7. This one has gotten more attention than average, scoring higher than 62% 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 267,751 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.