↓ Skip to main content

Targeting the cross-talk between Urokinase receptor and Formyl peptide receptor type 1 to prevent invasion and trans-endothelial migration of melanoma cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, December 2017
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#2 of 2,380)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
51 news outlets

Citations

dimensions_citation
18 Dimensions

Readers on

mendeley
13 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Targeting the cross-talk between Urokinase receptor and Formyl peptide receptor type 1 to prevent invasion and trans-endothelial migration of melanoma cells
Published in
Journal of Experimental & Clinical Cancer Research, December 2017
DOI 10.1186/s13046-017-0650-x
Pubmed ID
Authors

Concetta Ragone, Michele Minopoli, Vincenzo Ingangi, Giovanni Botti, Federica Fratangelo, Antonello Pessi, Maria Patrizia Stoppelli, Paolo Antonio Ascierto, Gennaro Ciliberto, Maria Letizia Motti, Maria Vincenza Carriero

Abstract

Accumulating evidence demonstrates that the Urokinase Receptor (uPAR) regulates tumor cell migration through its assembly in composite regulatory units with transmembrane receptors, and uPAR88-92 is the minimal sequence required to induce cell motility through the Formyl Peptide Receptor type 1 (FPR1). Both uPAR and FPR1 are involved in melanoma tumor progression, suggesting that they may be targeted for therapeutic purposes. In this study, the role of the uPAR-FPR1 cross-talk to sustain melanoma cell ability to invade extracellular matrix and cross endothelial barriers is investigated. Also, the possibility that inhibition of the uPAR mediated FPR1-dependent signaling may prevent matrix invasion and transendothelial migration of melanoma cells was investigated. Expression levels of uPAR and FPR1 were assessed by immunocytochemistry, Western Blot and qRT-PCR. Cell migration was investigated by Boyden chamber and wound-healing assays. Migration and invasion kinetics, trans-endothelial migration and proliferation of melanoma cells were monitored in real time using the xCELLigence technology. The agonist-triggered FPR1 internalization was visualized by confocal microscope. Cell adhesion to endothelium was determined by fluorometer measurement of cell-associated fluorescence or identified on multiple z-series by laser confocal microscopy. The 3D-organotypic models were set up by seeding melanoma cells onto collagen I matrices embedded dermal fibroblasts. Data were analyzed by one-way ANOVA and post-hoc Dunnett t-test for multiple comparisons. We found that the co-expression of uPAR and FPR1 confers to A375 and M14 melanoma cells a clear-cut capability to move towards chemotactic gradients, to cross extracellular matrix and endothelial monolayers. FPR1 activity is required, as cell migration and invasion were abrogated by receptor desensitization. Finally, melanoma cell ability to move toward chemotactic gradients, invade matrigel or fibroblast-embedded collagen matrices and cross endothelial monolayers are prevented by anti-uPAR84-95 antibodies or by the RI-3 peptide which we have previously shown to inhibit the uPAR84-95/FPR1 interaction. Collectively, our findings identify uPAR and FPR1 as relevant effectors of melanoma cell invasiveness and suggest that inhibitors of the uPAR84-95/FPR1 cross-talk may be useful for the treatment of metastatic melanoma.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 46%
Student > Bachelor 2 15%
Professor 1 8%
Unknown 4 31%
Readers by discipline Count As %
Medicine and Dentistry 3 23%
Biochemistry, Genetics and Molecular Biology 2 15%
Pharmacology, Toxicology and Pharmaceutical Science 2 15%
Immunology and Microbiology 1 8%
Engineering 1 8%
Other 0 0%
Unknown 4 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 403. 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 18 December 2017.
All research outputs
#73,840
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#2
of 2,380 outputs
Outputs of similar age
#1,659
of 445,594 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#1
of 43 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,380 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done particularly well, scoring higher than 99% 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 445,594 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 99% of its contemporaries.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.